Imbalances in Ca²⁺ are the most common examples of death routines using physiological signalling systems. Deregulation of Ca²⁺ signalling is involved in many types of cell death: it triggers excitotoxicity in neurones and muscle cells, it initiates apoptosis in many excitable and non-excitable tissues, and it acts as activator and executor of necrotic cell death. All these death subroutines use existing molecular systems, which are responsible for physiological Ca²⁺ signalling. As tissue plasticity and remodelling became a fundamental step in evolution of complex organisms, biochemical programmes involving complex cascades leading to cell disassembly have also developed. Intracellular calcium stores, the endoplasmic reticulum (ER) and mitochondria represent multifunctional organelles, intimately involved in various aspects of cellular activity. The disruption of Ca²⁺ homeostasis in both the ER and mitochondria can be involved in neurodegenerative disorders such as diabetic peripheral neuropathies and Alzheimer disease.