The first cult site was established here in the 7th century BC, dedicated to the worship of Apollo Maleatas.
From the 5th century BC onwards Asclepius came to stand alongside his mythological divine father, Apollo. As the people of Epidaurus succeeded in promoting their "asclepieion" as Asclepius´ birthplace, it developed into the god's most important sanctuary and amassed great wealth. It was the healing god Asclepius who drew pilgrims and those seeking cures to Epidaurus.
During the Roman period, the complex was supplemented by cisterns, wells, thermae and a building with a courtyard.
In 87 BC, the sanctuary was looted by the Roman general Sulla, who handed over numerous votive offerings and cult objects to his soldiers as pay. However, the sanctuary was rebuilt during the later Roman period.

In 395 AD the Goths under Alarich I raided the sanctuary. With the rise of Christianity, the ancient cult sites increasingly lost their significance. The site was "officially" closed in 426 AD.
Epidaurus has been a UNESCO World Heritage Site since 1988.