Non-self recognition resulting in programmed cell death is a ubiquitous phenomenon in filamentous ascomycete fungi and is termed heterokaryon incompatibility (HI). Recent analyses show that genes containing predicted HET domains are often involved in HI; however, the function of the HET domain is unknown. Autophagy is induced as a consequence of HI, whereas the presence of a predicted transcription factor, VIB-1, is required for HI. Morphological features associated with apoptosis in filamentous fungi are induced by various stresses and drugs, and also during HI. Future analyses will reveal whether common or different genetic mechanisms trigger death by non-self recognition and death by various environmental onslaughts.