Autophagy is a catabolic recycling pathway triggered by various intra- or extracellular stimuli that is conserved from yeast to mammals. During autophagy, diverse cytosolic constituents are enveloped by double-membrane vesicles, autophagosomes, which later fuse with lysosomes or the vacuole to degrade their cargo. Dysregulation in autophagy is associated with a diverse range of pathologies including cardiovascular disease, the leading cause of death in the world. Accordingly, there is tremendous interest in modulating autophagy for therapeutic purposes. One complexity with regard to cardiovascular homeostasis, however, is that the timing of autophagic activity appears to be critical; for example, cardiomyocyte autophagy during ischemia/reperfusion can be either beneficial or harmful. Here, we review the molecular mechanisms that govern autophagosome formation and analyze the link between autophagy and cardiovascular disease.