Mitochondria play a central role in apoptosis in mammalian cells. Bcl-2 family proteins regulate the release of proteins from the intermembrane space, which activate caspases and lead to cell death. The review discusses the extensive literature on proteins released from the intermembrane space and their roles in apoptosis. It also compares apoptosis pathways in Caenorhabditis elegans, Drosophila melanogaster, and mammals, highlighting remaining mysteries. The role of mitochondria in apoptosis is discussed, including the release of cytochrome c, Smac/DIABLO, Omi/HtrA2, and AIF. These proteins are essential for apoptosis execution. The review also addresses the role of mitochondria in invertebrate cell death, noting that while key regulators of apoptosis are conserved, the involvement of mitochondria in caspase activation is less clear in invertebrates. The review highlights the complexity of apoptosis pathways and the need for further research to understand the mechanisms involved.Mitochondria play a central role in apoptosis in mammalian cells. Bcl-2 family proteins regulate the release of proteins from the intermembrane space, which activate caspases and lead to cell death. The review discusses the extensive literature on proteins released from the intermembrane space and their roles in apoptosis. It also compares apoptosis pathways in Caenorhabditis elegans, Drosophila melanogaster, and mammals, highlighting remaining mysteries. The role of mitochondria in apoptosis is discussed, including the release of cytochrome c, Smac/DIABLO, Omi/HtrA2, and AIF. These proteins are essential for apoptosis execution. The review also addresses the role of mitochondria in invertebrate cell death, noting that while key regulators of apoptosis are conserved, the involvement of mitochondria in caspase activation is less clear in invertebrates. The review highlights the complexity of apoptosis pathways and the need for further research to understand the mechanisms involved.