Infection with microbial agents (bacteria, fungi, viruses and parasites) is a challenge to a host cell. The host cell's response to infection is complex and entails changes in the activity of a number of intracellular signalling pathways, commonly including the apoptotic machinery. Microbes, if they have evolved the capacity to infect mammals or other complex hosts, have to be able to deal with such defence systems. The lifestyle of microbes varies substantially – viruses, for instance, depend on an intact cell, whereas many bacteria grow on surfaces and are not sensitive to host cell apoptosis. What we know about microbial interference with host cell apoptosis is in accordance with these lifestyles. Viruses often directly target and inhibit the apoptosis machinery with specific proteins whereas other microbes frequently also interfere with host apoptosis but more indirectly. Key concepts: Microbes (bacteria, fungi, viruses and parasites) can vary widely in terms of growth requirements and intimacy of association with host cells. Apoptosis is commonly induced in cells infected with microbes. In infections with obligate intracellular agents, apoptosis can be a defence mechanism of the host cell. A number of viruses carry genes whose products can directly interfere with the host cell's apoptosis apparatus. Many cells become activated when encountering microbial agents, and this activation may entail the triggering of pro‐survival pathways in the host cell. Activation of antiapoptotic pathways in immune cells by microbial components is a regulatory mechanism of the immune response.