The religious order of St John originated in a hospital in Jerusalem. Although the exact date it opened is unknown, the Pope confirmed the new Order of the Hospital of St John of Jerusalem in 1113. Staffed by monks, the hospital offered medical care to sick pilgrims of all faiths and nationalities.

From the 1100s, the military side of the order assumed prime importance and secured pilgrim routes to and from holy places. Increasing wealth allowed the order to maintain its health-care functions. By this time, other orders, such as the Templars and Teutonic Knights, had also formed.

In the 1200s all of these Christian orders were driven from the mainland of the eastern Mediterranean and settled in Cyprus and Venice and, subsequently, in Rhodes and Malta where they built several large hospitals. The Sacred Infirmary in Malta was among the grandest and formed a school of anatomy and surgery in 1676. After losing Malta to Napoleon in 1798, the Order of St John descended into chaos, but confraternities survived throughout Europe.

In the 1800s members in England returned to their earlier health-care work. Influenced by the Red Cross, they provided care for battlefield casualties, as well as an early ambulance service. By 1902 the St John Ambulance Association, formed in 1877, had 12,000 volunteers. Based in London, the order re-established an ophthalmic hospital in Jerusalem in the 1880s, and once again offered medical services in its place of origin. Its clinic in Gaza today treats more than 50,000 patients annually.