His father, grandfather, and grandmother each died of the plague in the span of three days when Caravaggio was just six years old, and his mother succumbed to the disease four years later.

Boy Peeling Fruit was painted shortly after his arrival in Rome in 1592. The fruit being peeled by the boy is something of a mystery. While some critics suggest it may be a pear, it could also be a nectarine or plum, several of which lie on the table, but these are not usually peeled. Some have suggested a bergamot, a pear-shaped citrus fruit grown in Italy, but others object that the bergamot is sour and practically inedible.

While Caravaggio's extraordinary brand of realism would later become one of his most celebrated traits, at first it was much frowned upon. His subjects, replete with wrinkles, squints and defects, were a far cry from the fashionable idealism of Michelangelo. One of the painter's rivals accused him of creating paintings of "terrible naturalism ... astonishing deceptions, which attracted and ravished human sight."

In David with the Head of Goliath (1610), Caravaggio depicts himself as the severed head of Goliath dangling from David's hand. The model for David is il suo Caravaggino ("his own little Caravaggio"). This most plausibly refers to Cecco del Caravaggio, the artist's studio assistant in Rome some years previously, recorded as the boy "who lay with him."

Caravaggio employed close physical observation with a dramatic use of chiaroscuro that came to be known as tenebrism. He made the technique a dominant stylistic element, darkening shadows and transfixing subjects in bright shafts of light.

In the late 16th and early-17th centuries, the Catholic Church was in the middle of a campaign known as the Counter Reformation that was meant to counter the growing threat of Protestantism. As part of this program, the Church turned to painters like Caravaggio to visually confirm the dominance and power of Catholicism and woo back Catholics who had converted to Protestantism.

It wasn't only his paintings that were brutal and violent. Caravaggio went to trial at least 11 times for things like writing libelous poems, throwing a plate of artichokes at a waiter, and attacking people with swords. He eventually fled Rome to escape punishment for killing Ranuccio Tommasoni. The barber surgeon's report for Tomassoni's death reported that he bled out through the femoral artery in his groin, suggesting Caravaggio had tried to castrate him, which in turn suggests the fight was over a woman.

Hoping to secure a pardon for Tomassoni's death, Caravaggio joined the Knights of Malta, but soon after he was expelled "as a foul and rotten member" after attacking and badly injuring another knight.

Nativity with St. Francis and St. Lawrence has been missing since 1969 when it was stolen from the Oratory of Saint Lawrence in Palermo. Although the work has never been found, members of the Italian mafia have claimed that the painting was frequently displayed at major meetings and gatherings of high-ranking mafia members, but that it was subsequently destroyed. A replica was commissioned in 2015 and now hangs in the altar.

The Beheading of Saint John the Baptist is his largest work and the only painting to which he put his signature, which spills in red blood from the Baptist's cut throat.