14- 3- 3 proteins are abundantly expressed in the brain and have been detected in the cerebrospinal fluid of patients with different neurological disorders. Although the function of this family of highly conserved proteins is not completely known, recent evidence indicates their involvement in multiple cellular processes. By their interaction with more than 100 binding partners, 14- 3- 3 proteins modulate the action of proteins that are involved in cell cycle and transcriptional control, signal transduction, intracellular trafficking and regulation of ion channels. The study of some of these interactions is sheding light on the role of 14- 3- 3 proteins in processes such as apoptosis and neurodegeneration.