Chronic and age-related neurodegenerative diseases are characterised by a selective loss of specific subsets of neurons over a period of years. The underlying causes of these diseases are not clear, however, the death of neurons and the loss of cell-cell contacts seem to be key features. Understanding molecular mechanisms that control neuronal cell death and survival and identification of factors involved in these processes is crucial for the development of preventing strategies and further treatment of neurodegenerative disorders. In the present review accumulated evidence is presented that members of a ubiquitous family of annexins, homologous Ca2+- and membrane-binding proteins expressed in the central nervous system (CNS), are playing a role in regulation of neuron life span, as either potent neuroprotective or proapoptotic agents. It was also found that annexins might be related to some CNS pathologies and disorders. In addition, annexins are important partners in many vital neuronal processes, as they exhibit neurotransmitter precursor- and nucleotide-binding properties in vitro, interact with nucleotide-binding proteins in brain, as well as are involved in the cellular response to inflammation and oxidative stress. These properties suggest that some annexins may couple calcium homeostasis and cellular metabolism in neurons and neuroendocrine cells.