Apoptosis is an evolutionary-conserved physiological mechanism to remove cells from an organism. Cellular apoptosis is mediated via an intracellular signalling programme that involves a variety of signalling molecules and cellular organelles including caspases, sphingomyelinases, Bcl-2-like proteins and proteins to cleave the DNA and mitochondria. Mitochondria contain several pro-apoptotic molecules that activate cytosolic proteins to execute apoptosis, block anti-apoptotic proteins in the cytosol and directly cleave nuclear DNA. Mitochondria trap these pro-apoptotic proteins and physically separate pro-apoptotic proteins from their cytoplasmic targets. Apoptosis is then initiated by the release of mitochondrial pro-apoptotic proteins into the cytosol. This process seems to be regulated by Bcl-2-like proteins and several ion channels, in particular the permeability transition pore (PTP) that is activated by almost all pro-apoptotic stimuli. Experimental Physiology (2003) 88.1, 85-90.