Apoptosis is a morphologically distinct form of programmed cell death that plays important roles in development, tissue homeostasis and a wide variety of diseases, including cancer, AIDS, stroke, myopathies and various neurodegenerative disorders (see Thompson (1995) for review). It is now clear that apoptosis occurs by activating an intrinsic cell suicide program which is constitutively expressed in most animal cells, and that key components of this program have been conserved in evolution from worms to insects to man. Genetic studies of programmed cell death in experimentally highly accessible invertebrate model systems have provided important clues about the molecular nature of the death program, and the intracellular mechanisms that control its activation. This review summarizes some of the key findings in this area, but also touches on some of the many unresolved questions and challenges that remain.