SUMOs (Small Ubiquitin-like modifiers) belong to a superfamily of ubiquitin like proteins (Ubls) that are covalently conjugated to their substrates via enzymatic cascade reactions. The heterodimeric activating complex (SAE1/SAE2, E1) and conjugating enzyme (Ubc9, E2) required for the SUMO conjugation pathway are distinct from those involved in other Ubl pathways, and the presence of ligases (E3) stimulates the conjugation reaction. SUMO is implicated in a variety of physiological as well as pathological processes such as cell division, signal transduction, DNA damage and repair, and cancer development. This review focuses on the fundamental features of SUMO conjugation and its potential implication in cardiovascular development.