Historically known as Insula Inter Duos Pontes ("Island Between Two Bridges"), Tiber Island has been a significant site since at least the 3rd century BCE. Also known as the Insula Tiberina in Latin, it was associated with healing and medicine began with the establishment of the Temple of Aesculapius in 291 BCE, following a devastating plague in Rome. The island's prominence continued not only through the Republican period but also Roman Empire period, the Middle Ages, and into the modern era, where it remains a testament to Rome's layered history.

There is a legend which says that after the fall of the hated tyrant Tarquinius Superbus (509 BCE), the angry Romans threw his body into the Tiber. His body then settled onto the bottom where dirt and silt accumulated around it and eventually formed Tiber Island. Another version of the legend says that the people gathered up the wheat and grain of their despised ruler and threw it into the Tiber, where it eventually became the foundation of the island.

Tiber Island’s natural structure is remarkable both for its geological formation and for the role it played in shaping human use over millennia. The island is composed primarily of alluvial deposits carried down by the river Tiber, forming a slightly elongated, boat-shaped landmass approximately 270 meters long and 67 meters wide. Its raised profile, relative to the surrounding riverbed, made it a natural refuge during seasonal floods, while the river’s gentle bifurcation around the island created two distinct channels that facilitated both navigation and defense. The long, narrow shape of the island naturally delineated areas for settlement, shrines, and later hospital facilities, while the curvature of its banks enabled the construction of quays and embankments that could accommodate both ritual processions and practical river traffic.

Over centuries, Roman engineers supplemented the island’s natural architecture with travertine revetments and embankments, preserving its integrity against erosion and shaping it to resemble a ship—a symbolic gesture tied to its cultic association with Aesculapius—yet the underlying island remained entirely a product of fluvial processes, reflecting the Tiber’s sedimentary dynamics and demonstrating how natural landforms can dictate both religious and civic planning in a riverine urban environment.

The earliest recorded use of Tiber Island dates to the early 3rd century BCE. In 293 BCE, a plague prompted the Roman Senate to consult the Sibylline Books, which advised the construction of a temple to Aesculapius, the Greek god of healing. A delegation was sent to Epidaurus to retrieve a statue of the deity; upon their return, a snake, sacred to Aesculapius, allegedly slithered off the ship and onto the island. Interpreting this as a divine sign, the Senate established the temple on the island in 291 BCE. The island was subsequently shaped to resemble a ship, with travertine facing and an obelisk erected at its center, symbolizing the mast. This transformation underscored the island's association with the god of healing.

Over time, the island became a hub for various religious cults, including those dedicated to Jupiter Jurarius, Semo Sancus, Gaia, Faunus, Vejovis, Tiberinus, and Bellona. These deities were worshipped through shrines established on the island, reflecting its multifaceted religious significance.

During the medieval period, the island's importance persisted. In 998 CE, Emperor Otto III commissioned the construction of the Basilica of San Bartolomeo all'Isola, which incorporated remnants of the ancient temple. The Fatebenefratelli Hospital, founded in the 16th century CE, further solidified the island's association with medicine.

Temple of Aesculapius
Constructed between 293 and 290 BCE, the Temple of Aesculapius was dedicated in 289 BCE. The temple's establishment followed a plague in Rome and was based on a directive from the Sibylline Books. A delegation was sent to Epidaurus to retrieve a statue of Aesculapius, and during their return journey, a snake, sacred to the god, allegedly slithered off the ship and onto the island. This event was interpreted as a divine sign, leading to the temple's construction on the island. The island was subsequently shaped to resemble a ship, with travertine facing and an obelisk at its center, symbolizing the mast. The temple served as a center for healing, attracting those seeking cures for various ailments. Carving of a snake (inspect) around a staff is still visible on the surviving structure.

Basilica of San Bartolomeo all'Isola
Built in 998 CE by Emperor Otto III, the Basilica of San Bartolomeo all'Isola was constructed on the site of the ancient Temple of Aesculapius. The basilica was part of a broader effort to revitalize Rome's religious institutions during the medieval period. Architecturally, the basilica reflects the transition from ancient Roman to medieval Christian designs, incorporating elements from the earlier temple. The church remains active today and houses relics of St. Bartholomew, further linking the site to its historical and mythical roots.

Fatebenefratelli Hospital
Founded in the 16th century, the Fatebenefratelli Hospital is located on Tiber Island (Ospedale Isola Tiberina - Gemelli Isola) and continues to operate as a medical facility. Its establishment reaffirmed the island's long-standing association with medicine and healing. The hospital's presence underscores the continuity of the island's role in healthcare, from ancient religious healing practices to modern medical care.

Ponte Fabricio
Completed in 62 BCE, the Ponte Fabricio is the oldest extant bridge in Rome. Commissioned by Lucius Fabricius, a Roman official, the bridge connects Tiber Island to the Rione Sant'Angelo. Constructed of stone and rock, the bridge spans two arches and has remained in continuous use since its completion. The bridge's enduring structure and functionality highlight the advanced engineering skills of ancient Rome. The Ponte Fabricio, the only original extant bridge from ancient Roman period, connects the island from the northeast to the Field of Mars in the modern day rione Sant'Angelo (left bank).

Ponte Cestio
Built around 46 BCE by Lucius Cestio, the Ponte Cestio links Tiber Island to the Trastevere district. The historic strcuture of the bridge was contemporary with the Ponte Fabricio, reflecting the Roman emphasis on connectivity and infrastructure. Over the centuries, the Ponte Cestio has undergone several reconstructions, with significant rebuilding in the 19th century CE. Despite these changes, portions of the original structure remain, offering insights into Roman bridge construction techniques. The Ponte Cestio, of which only some original parts survived, connects the island to Trastevere on the south (right bank).