Apoptosis is used by metazoan organisms to dispose of damaged or unnecessary cells during development, tissue homeostasis, and disease. One of the situations where apoptosis is important is in defense against microbial pathogens, especially viruses. The demonstration that apoptosis could be stimulated by baculovirus infection was one of the first examples of apoptosis associated with virus infection, and this system remains one of the most valuable for studying how apoptosis can be a defense against viruses. In addition, studying how baculoviruses regulate apoptosis has led to many important findings in the field of apoptosis research, such as the discovery of P35, a caspase inhibitor that is widely used in studies of apoptosis, and IAP (inhibitor of apoptosis) proteins, which have homologs in cellular genomes that play important roles in regulating apoptosis and cytokinesis. This review highlights the range of apoptotic responses observed between different baculoviruses and different lepidopteran insects, and the diverse baculovirus genes that have evolved to regulate apoptosis.