AbstractViruses control the host cell by exploiting its molecular machinery to facilitate viral replication and propagation. Understanding different viral mechanisms and biochemical pathways is crucial for finding promising therapeutic solutions to viral infections. The mitochondrion is a vital organelle targeted by various types of viruses. More specifically, viruses interact with the voltage‐dependent anion channel (VDAC), a porin protein found in the outer mitochondrial membrane. VDAC controls metabolite flux, regulates reactive oxygen species production, and promotes mitochondrial‐mediated apoptosis by releasing pro‐apoptotic proteins. Hence, a common pathogenic strategy used by many viruses seems to exploit natural pathways that VDAC regulates. This review aims to address the inhibition and enhancement roles of VDAC in viral pathogenesis and outlines multiple links and interactions between VDAC and viral proteins as potential antiviral targets.