A partire dal III secolo avanti Cristo il mondo classico cede il testimone all'ellenismo. Nuove correnti di pensiero permeano l'universo culturale del tempo: il cinismo, l'epicureismo e lo stoicismo. Tra il I e il II secolo dopo Cristo la lezione del pensiero greco raggiunge Roma e contagia Seneca e Marco Aurelio, l'imperatore filosofo.
Reale was born in Candia Lomellina, Pavia. He attended the Gymnasium and the Liceo classico of Casale Monferrato, and was then educated at the Università Cattolica del Sacro Cuore of Milan, where he graduated. He later continued his studies in Marburg an der Lahn and Munich. After a period of teaching in high schools, he won a professorship at the University of Parma, where he taught courses in moral philosophy and the history of philosophy. He then returned to the Università Cattolica del Sacro Cuore of Milan, where he was professor of the history of ancient philosophy for many years, and where he also founded the Centro di Ricerche di Metafisica. In 2005 he moved to teach at the new faculty of philosophy at Vita-Salute San Raffaele University of Milan.