Apoptosis is implicated in a number of diseases, including neurodegenerative diseases and AIDS. More and more, evidence is accumulating pointing to the critical role of ceramides in the induction of apoptosis. The present review summarizes (i) the molecular basis and regulation of the apoptotic machinery, (ii) the molecular role of ceramides in the induction or execution of apoptotic pathways, and (iii) evidence linking ceramide generation to various apoptotic diseases. Additionally, this review discusses putative therapeutic approaches inhibiting ceramide production in apoptotic diseases.