It has recently become clear the role played by alterations in apoptosis during the development of several chronic diseases (i.e. inflammatory, neurodegenerative and neoplastic pathologies). For this reason, the research for possible therapeutic strategies involving the modulation of the apoptotic pathways has attracted considerable interest in the past few years. In particular, it has been shown that apoptosis may be induced or inhibited by a variety of nutritional compounds providing health benefits. The aim of this review is to examine the ability of different dietary polyunsaturated fatty acids (PUFAs) to induce apoptosis, especially in the cancer field. The molecular effects of different PUFAs found in dairy products, meat, fish, vegetable seeds and oils, and known to affect the incidence and progression of cancer and other chronic diseases, will be analyzed. To this aim, our effort will concentrate in critically reviewing the published works concerning the effects of: (a) the n-6 PUFAs gamma-linolenic acid, arachidonic acid, and conjugated linoleic acid; (b) the n-3 PUFAs eicosapentaenoic acid and docosahexaenoic acid on the apoptotic process. We will also pay attention to the recent findings regarding the possible role of PUFAs as regulators of the endoplasmic reticulum stress-pathway of apoptosis.