Ca(2+) regulates many steps in cell death mechanisms, and is potentially involved in all types of cell death. Moreover, virtually all elements of the cellular Ca(2+) toolbox seem to contribute to remodeling of the Ca(2+) signaling machinery during cell death processes. As expected from the ubiquitous nature of Ca(2+) signaling, these mechanisms are operative in all cell types, and their malfunction may lead to a wide diversity of pathological implications. The contributions in this Special Issue deal with many different aspects of the relation between Ca(2+) signaling and cell death. They illustrate the complexity of this relation, and importantly they give an outlook on potential new therapeutic targets for treatment of diseases connected to defects in cell death pathways.