An obsessive, impassioned sex addict, Florentino falls madly in love with Fermina Daza on sight. After a brief love affair during which he sees Fermina only in passing, he cannot accept that she has rejected him, and dedicates his life to one day winning back her love. In the fifty-one years, nine months, and four days after their troubled love affair ends, he eagerly awaits the death of Fermina's husband, Dr. Juvenal Urbino. Despite his undying love for Fermina, he sleeps with innumerable women, though he remains convinced that he is saving himself for her, for he can never love another woman the way he loves Fermina. Florentino uses sex as an addict would a narcotic; it is the one means by which he is able to forget his heartache and his desire for Fermina, the woman who is the source of all his anguish.

His lovesickness for Fermina is often equated to cholera, as he is literally plagued by his passion for her. He is insane with love, and exhibits obsessive, borderline criminal behavior. He stalks Fermina and keeps watch on her house. He is drunk with his passion for her, and can think of nothing else. At work, he is incapable of writing a business letter; he can only write poetic prose as he writes in his love letters to her. He thrives on his plague of love, and revels in his own suffering; he feels martyred when he is thrown in jail for serenading Fermina with his violin. When Lorenzo Daza threatens to shoot him, he challenges him, saying that it is most noble to die for love. Ultimately, he is determined to win Fermina's affections, and will stop at nothing to attain them. At once, he is the novel's antagonist and protagonist, for he may be madly in love or simply mad.