Apoptosis has been considered to be a host defense mechanism against viral infection in multicellular organisms. This is based on the findings that apoptogenic mutants of insect viruses cannot grow because infected host cells die by apoptosis. This suggests that the apoptotic response of host cells has a deleterious effect on virus infection. Thus, apoptosis is an important host defense mechanism that is capable of inhibiting viral replication during infection. However, in vitro studies indicated that apoptosis alone does not provide the same protection against viral infection in animal cells as it does in the insect cells. Still, most animal viruses have acquired a strategy to overcome host cell apoptosis. In addition, a varying degree of necrosis usually accompanies apoptosis, suggesting a possible contribution of necrosis to the host reactions against virus. To understand the physiological significance of apoptosis during animal virus infection, we have characterized viral growth and the cellular responses against virus infection in a wide variety of virus-cell interaction systems. Mainly based on our own works, we discuss the nature of apoptosis in the animal virus infection and verify its role as a host defense mechanism against virus infection.