The cardiac proteasome is increasingly recognized as a complex, heterogeneous, and dynamic organelle contributing to the modulation of cardiac function in health and diseases. The emerging picture of the proteasome system reveals a highly regulated and organized molecular machine integrated into multiple biologic processes of the cell. Full appreciation of its cardiovascular relevance requires an understanding of its proteolytic function as well as its underlying regulatory mechanisms, of which assembly, stoichiometry, posttranslational modification, and the role of the associating partners are increasingly poignant.