Beclin-1 (Bcl-2 interacting coiled-coil protein; ATG6) is a multifunctional protein, well-known as a key regulator of autophagy and required for the initiation step in autophagosome formation. It interacts with several cofactors (Atg14L, UVRAG, Bif-1, rubicon, Ambra1, HMGB1, nPIST, VMP1, SLAM, IP3R, PINK and survivin) to regulate the lipid kinase PI3K protein and promote formation of PIK3C3/VPS34-containing complexes. These interactions induce autophagy, which is a process of programmed cell survival increased during periods of cell stress and extinguished during the cell cycle. Furthermore, beclin-1 is implicated in numerous biological processes, including adaptation to stress, development, endocytosis, cytokinesis, immunity, infection, tumorigenesis, aging and cell death. Beclin-1 is tightly regulated by diverse mechanisms, such as epigenetic silencing, microRNA regulation, post-translational modifications and protein-protein interactions. Multiple diseases are associated with deficiency or malfunction of beclin-1, including cancer and neurodegeneration.