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Natural Killer (NK) cells are important in the elimination of virally-infected and cancer cells. NK cell recognise changes in surface molecules on cells, which can cause an NK cell to kill the target cell by either ligation of death receptors or perforin-mediated release of granzymes. Granzymes are serine proteases that cleave numerous cellular proteins that are important in co-ordinating cell death in the target cell. Induction of apoptosis involves dysregulation of cellular machinery including disruption of mitochondrial membrane potential, nuclear fragmentation and cell membrane permeability. Here I have analysed the differences in NK cell susceptibility of human cells transformed with either the adenovirus species A (Ad12) or adenovirus species C (AdS) El regions, as well as looking at the mechanisms of how a cancer cell could become resistant to NK cell-mediated killing.