To date much attention has been focused on regulation of apoptosis in proliferating cells. However, recent evidence shows that regulation of apoptosis in quiescent tissue plays an important role in homeostasis of the organism. This review examines the implications of apoptosis of quiescent cells for both tumourigenesis and viral infection such as HIV. In this article we propose a dual role for cellular activation in the homeostasis regulation. In this model cellular mitogens not only activate quiescent cells into the active cell cycle, but under certain conditions, loss of quiescence may result in apoptosis. The loss of quiescence-associated apoptosis may play a significant role in tumourigenesis and viral infections.