The voltage-dependent anion channel (VDAC) is a pore located at the outer membrane of the mitochondrion. It allows the entry and exit of numerous ions and metabolites between the cytosol and the mitochondrion. Flux through the pore occurs in an active way: first, it depends on the open or closed state and second, on the negative or positive charges of the different ion species passing through the pore. The flux of essential metabolites, such as ATP, determines the functioning of the mitochondria to a noxious stimulus. Moreover, VDAC acts as a platform for many proteins and in so doing supports glycolysis and prevents apoptosis by interacting with hexokinase, or members of the Bcl-2 family, respectively. VDAC is thus involved in the choice the cells make to survive or die, which is particularly relevant to cancer cells. For these reasons, VDAC has become a potential therapeutic target to fight cancer but also other diseases in which mitochondrial metabolism is modified. This article is part of a Special Issue entitled Mitochondria in Cancer, edited by Giuseppe Gasparre, Rodrigue Rossignol and Pierre Sonveaux.