Apoptosis is a normal aspect of human physiology ensuring tissue homeostasis. Evasion of endogenous cell death processes, including apoptosis, represents one of the characteristics of cancer. Defects in the physiological mechanisms of apoptosis contribute to the pathological cell expansion and to the development and progression of cancer. Resistance of malignant cells to cancer therapeutic agents may be, in some cases, caused by dysregulation of apoptotic pathways, e.g. BCL2 or IAP overexpression. The understanding of the physiological mechanisms that control apoptosis and the elucidation of apoptotic defects in cancer cells may lead to the development of targeted cancer therapies. Apoptotic pathways, molecules involved in the cross-talk between individual apoptosis pathways and promising new anti-cancer agents, which trigger directly or indirectly apoptosis of hematologic cancer cells, are reviewed in this article.