During cell culture, mammalian cells are exposed to numerous external and internal insults such as nutrient depletion, toxin accumulation, and external shear stress.  These events can sometime cause the cells to trigger apoptosis in which the cells actively participate in their own demise. The apoptosis cascade decreases the number of viable cells in a bioreactor and leads to the premature termination of cell culture runs.  Cell death may also lower productivity since bioreactor resources must be utilized to replace dead or dying cells.  A number of natural anti-apoptosis genes have been identified in both eucaryotes and viruses and these anti-apoptosis proteins are being used to block or limit the cell death cascade.  Unfortunately, these anti-apoptosis proteins can be degraded in culture or otherwise eliminated.  In order to increase their activity, some of the anti-apoptosis proteins can be modified to limit degradation in cell systems.  In addition, apoptosis pathways include feedback and feedforward loops that lead to amplification of the apoptotic response.  Strategies that block cell death at multiple points along the cascade may limit the amplification of these apoptotic signals. The role of bioprocess environments is also being examined by investigating survival of cells with anti-apoptosis genes in different bioreactors including batch, fed batch and perfusion.  The use these various bioprocess operating conditions will allow cell culture engineers to examine the relationship between anti-apoptosis engineering,  cell survival and physiology, and productivity for different mammalian cell systems.