Resistance to apoptosis is closely linked to tumorigenesis, as it enables malignant cells to expand even in a stressful environment. Cells resistant to apoptosis are also assumed to be resistant to anti-cancer therapies. Apoptosis has therefore taken a central position in cell death research. However, its contribution to treatment success is highly debated for solid tumors. It becomes more and more clear that cells can also die by non-apoptotic mechanisms, such as autophagy, mitotic catastrophe and necrosis. In this review, we summarize the current knowledge regarding the molecular pathways that underlie these apoptotic and non-apoptotic death pathways, and discuss the clinical data that have now accumulated to evaluate their roles in tumor development and cancer treatment.