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The notion of dignitas hominis is one of the most pervasive and long-lasting topoi in the traditional representation of the early Renaissance. In order to reconstruct the different strands of the debate about mankind in the fifteenth and sixteenth centuries, however, humanist and religious works on the “misery” of human condition also need to be taken into consideration. In these pages, a general overview on this subject is given, with a description of the key issues discussed in these texts and of their classical and Christian sources. Also, three humanist works (Leon Battista Alberti’s Theogenius, Poggio Bracciolini’s De miseria humanae conditionis, and Giannozzo Manetti’s Dialogus consolatorius) are compared and contrasted, especially from the viewpoint of the style, characters, and aims of these dialogues, so as to present three different approaches to the problem of human wretchedness and frailness.