The Decameron by Giovanni Boccaccio preserves important information about the plague outbreak in 1348 in Florence, Italy. The first thing he mentions is that people wondered if the cause of the plague was a malign influence of the planets or God's punishment of Florence for the sinfulness of its people.

The first action the people take is attempts at prevention, specifically "keeping the city clear from filth, and excluding all suspected persons" as well as praying and conducting special processions to try to persuade God to intervene to prevent or halt the spread of the plague.

Next, doctors, including many women and many quacks, attempted to discover and promot various cures, but none were effective. People soon discovered that the plague spread not just by close contact with a sick person but even by contact with a sick person's discarded clothing or bedding.

Because of the ease of transmission of the plague, healthy people began avoiding the sick; Boccaccio states:

These accidents [transmission of plague from clothing to animals], and others of the like sort, occasioned various fears and devices amongst those people that survived, all tending to the same uncharitable and cruel end; which was to avoid the sick, and everything that had been near them; expecting by that means to save themselves.

The ensuing panic as the plague continued to spread caused people to react in several ways. One group, because they considered the plague impossible to avoid, indulged in every form of pleasure and debauchery, in anticipation of their inevitable demise. Others isolated themselves in their houses and followed various strict medical regimes and forms of asceticism. Others, including the ones who were the protagonists of the Decameron, left the city to escape the plague, often moving to remote villas in the countryside and isolating themselves as much as possible. Corpses were left out in front of houses, with the dead no longer being honored or given elaborate funerals because of the many people who regarded isolation as the only precaution that could guard against the plague.