Cell shrinkage and dehydration are essential characteristics of apoptosis, and the loss of as much as half of the initial cell volume is not uncommon. This phenomenon is usually explained by the efflux of potassium and chloride ions. We reexamine this hypothesis based on the available data for ion concentrations and taking into account the requirements for osmotic equilibrium and electroneutrality. In addition to ion loss, the possible impacts of several other processes are discussed: the efflux of low-molecular osmolytes, acidification of the cytosol, the effects of water channels and pumps, heterogeneity of intracellular water and dissociation of apoptotic bodies. We conclude that most mammalian cells are theoretically capable of reducing their volume by 15-20% through ion loss or a decrease in cytosolic pH, although in reality the contribution of these mechanisms to apoptotic shrinkage may be smaller. Transitions between osmotically active and inactive water pools might influence cell volume as well; these mechanisms are poorly understood but are amenable to experimental study. Dissociation of apoptotic bodies is a separate mechanism of volume reduction; it should be monitored closely, which can be best achieved by measuring intracellular water rather than cell volume.