Since cell death by apoptosis plays a key role in the regulation of tissue homeostasis, dysregulation of the cells intrinsic death program may foster tumor formation and progression. “Inhibitor of apoptosis proteins” (IAPs) block apoptosis at the core of the apoptotic machinery by inhibiting effector caspases. Aberrant expression and/or function of IAPs are found in many human cancers and have been implied in resistance to current treatment approaches. Recent insights into the role of IAPs have provided the basis for various exciting discoveries that aim at modulating expression or function of IAPs. Thus, targeting IAPs, e.g. by antisense approaches or small molecule inhibitors, presents a promising novel approach for future drug development and may proof to be a successful strategy to overcome apoptosis resistance of human cancers.