After colonization or invasion, intracellular pathogens seek host cells to establish infections and facilitate replication. This lifestyle provides essential nutrients and protection from immune systems. Several host cells—in particular professional phagocytes, such as monocytes, macrophages, and neutrophils—have developed antimicrobial mechanisms to deplete the replicative niche of these intracellular microbes. Programmed cell death pathways are frontline defense mechanisms, whereby host cell suicide blocks intracellular microbial replication and exposes them for immune attack [1]. Recent advances have uncovered several programmed cell death pathways that are highly regulated to ensure proper immune responses. Besides canonical apoptosis, which initially preserves host cell integrity and is largely anti-inflammatory, macrophages can induce pyroptosis and necroptosis, which are both highly lytic and trigger proinflammatory signals (Figure 1). Pyroptosis depends on the cysteine-aspartic proteases, caspase-1 or caspase-11, which are activated by cytosolic pattern recognition receptors [1, 2]. Necroptosis is regulated by the TNFR (tumor necrosis factor receptor)-associated kinases, Ripk1 and 3, and is executed by MLKL (mixed lineage kinase domain-like)[3]. Successful intracellular pathogens must suppress programmed cell death signals during the replicative or latent phase but can potentially induce these signals to promote egress and dissemination. The timing and specificity of the cell death signal can dramatically influence pathogen or host survival, suggesting a complex interplay exists between inducing potent immunity and promoting pathogen egress. Most work in this area has focused on bacteria and parasites, but more recent studies have provided exciting evidence that fungal pathogens likewise modulate host cell death pathways.