The medieval town of Rhodes developed on part of the Hellenistic city in the northern tip of the island. Written sources mention -and archaeology has confirmed- the presence of a fortress protecting the population from enemy raids in the 7th century AD. The Early Byzantine town enclosed only a fraction of the later settlement, which in Hospitaller times was known as the Collachio. In the late 11th or the 12th century the walls expanded to enclose a suburb.

After the establishment of the Knights of St. John on the island in 1309, the defences were modified and expanded again to four times its Byzantine size to occupy a crescent of 42 hectares around the main harbour. The new walls were gradually adapted to meet the needs of gunpowder warfare.

The town was divided by its fortifications into three main parts: the Collachio or upper town was divided from the borgo or lower town where most civilians lived by a wall and moat. The Collachio contained the dwellings and most of the administrative buildings of the Knights and the last line of defence- the fortified palace of the Grand Master. The principal street of the Collachio, the Street of the Knights, joined the Palace with the Latin cathedral of Rhodes, Santa Maria del Borgo and its sides were lined with the inns of the various tongues of the Knights, the conventual church of the Order, the hospital, the chapel of St. Michael (now Holy Trinity). The rest of the population lived in the borgo, which was crossed by the high street (magna et comunis platea) which led to two important Hospitaller buildings- the church of Santa Maria del Borgo and the Hospice of St. Catherine.