The 350 letters composing the Rerum familiarum libri were written between 1325 and 1366. The event that led Petrarch to think of assembling them in one volume occurred in 1345, when he rediscovered in the Cathedral Library of Verona the corpus of letters Cicero had written to Atticus, Quintus, and Brutus. These letters, along with Seneca's Epistle to Lucilius, gave him the impulse to compose the Familiares in a volume. It was meant to be taken mainly as a book of instruction for daily living.

Much like Cicero and Seneca, Petrarch throughout dispenses prescriptions about questions of ethics: the value of moderation and chastity, the rewards of friendship, rules for dining, care about the condition of far-away friends, tranquillity of mind, how to contain feelings of anxiety about the flight of time, praise of the solitary life, cultivation of body and soul, appeals to peace, on how to bear grief, how to exercise virtue in the face of fortune's adversity, avoid suffering, offer consolation for death, and so forth. But because a book of ethics, a term to be understood as the art of living, can only emerge out of the texture of one's life, Petrarch includes in his collection accounts of what he himself has actually lived through. The slices of his life range from an experience such as mountain climbing, or taking walks among the ruins of the Roman Forum, to countering malevolent gossip about his personal reputation (especially the general suspicions about his purported envy toward Dante). On occasion he treats subjects that belong to the arena of politics or public discourse, such as Cola di Rienzo's quest for power that ended tragically, defenses of poetry and oratory, the need for reform of the papal curia, or even reflections on time-honored themes, such as the desirable form of the education of the prince.