The present study highlights the history of lazarettos in Candia (modern Heraklion, Crete, Greece), which was the most important Venetian possession in the Mediterranean at the time, while at the same time it recounts the terrible plague which went down in history as the Great Plague of Candia (1592-1595). The study will also attempt to give a satisfactory answer to the epidemiological questions raised by the worst epidemic that Crete had experienced since the era of the Black Death in the 14th century. The city was about to lose more than a half of its population (51.3%), although it was saved from complete annihilation by the composure, courage and inventiveness of its Venetian commander, Filippo Pasqualigo, whose report to the Venetian Senate makes an invaluable source of information regarding the events of this dramatic period. Candia would also witness the emergence of typical human reactions in cases of epidemics and mass deaths, such as running away along with the feeling of self-preservation, dissolute life and ephemeral pleasures, as well as lawlessness and criminality. The lazaretto proved inefficient in the face of a disaster of such scale, whereas the epidemic functioned as a "crash-test" for the Venetian health system. Eventually, in an era when the microbial nature of the disease was unknown, it seems that it was practically impossible to handle emergency situations of large-scale epidemics successfully, despite strict laws and well-organized precautionary health systems.