Cell death by apoptosis usually occurs in a regulated, limited fashion. Only selected target cells are deleted in the process of ontogeny, development and regeneration. In contrast, under pathophysiological conditions, apoptosis imposes as a massive, chaotic, non-selective event that may occur for periods or even up to decades. It is likely that apoptosis is the initial cellular response to injury and may thus initiate several, intertwined cellular and cytokine cascades that culminate in tissue injury, inflammation, fibrosis and finally, in cirrhosis. Obviously, this cascade of events is of particular importance in various types of acute and chronic liver diseases. In contrast, defective apoptosis and increased cell proliferation is associated with cancer. Indeed, tumor cells often show alterations in genes regulating the apoptosis machinery. This overview is focused on the role of apoptosis in select important liver diseases. Today, rational-based strategies are being developed to either promote or suppress apoptotic cell death as a novel therapeutic option in the treatment of these liver diseases.