The processes of dying are as tightly regulated as those of growth and proliferation, and together they establish a finely tuned balance that ensures proper organ size and function. Failure in the regulation of these responses lies at the heart of many human diseases. Certain members of the inhibitor of apoptosis (IAP) protein family function as important gatekeepers of cell death and survival. While IAPs can regulate cell death by controlling caspases, they also modulate other signalling processes that impact on cell viability. Probably the most important contribution of IAPs to cell survival and tumorigenesis resides in the ability of a number of IAPs to act as ubiquitin-E3 ligases regulating NF-κB signalling. Here, we discuss the latest insights into the ubiquitin-related roles of IAPs and how this contributes to the survival of cells and the organism.