To treat the ever growing number of obese patients, reduction of adipocyte number by apoptosis may complement other therapeutic options. On the other hand in free fat grafts, apoptosis along with necrosis is responsible for long term volume reduction. To ensure successful soft tissue reconstruction it is mandatory to keep apoptosis on a low level in adipocytes, adipose-derived stromal cells and others cells of the fat graft. Apoptotic pathways have been sufficiently studied in various tissues, but the knowledge about apoptotic pathways in adipocytes is surprisingly scarce. Current knowledge about apoptotic pathways in adipose tissue is elaborately reflected in this review as well as the association of cancer with obesity. Possibilities to induce and reduce adipose tissue apoptosis in animal models are discussed as well as clinical implications of fat cell apoptosis. Mechanisms of apoptosis induction have been studied in animal models and suggest that a tight control of apoptosis induction is necessary because otherwise detrimental metabolic effects of fat mass loss will occur that may mimic lipodystrophic diseases. At present, targeted induction of adipocyte apoptosis appears to be of some concern related to increased blood lipid concentrations, ectopic lipid storage and other detrimental metabolic effects. Treatment of autologous adipocytes used for lipofilling procedures with appropriate substances may result in more satisfactory long-term outcomes as well as stimulation of stem cell differentiation in a strictly local manner.