Vascular anomalies can present both as the dominant or less prominent feature of multisystem syndromes. In this review, we describe some of the more notable disorders. They may arise as a consequence of a sporadic somatic mutation or less frequently, familial germline mutations. We discuss their clinical features focusing on the prominent vascular anomaly (e.g., infantile haemangioma, capillary malformation, venous malformation) as a first diagnostic clue, current understanding of their genetic basis and outline further investigations as well as management. Many of these syndromes present with variable and overlapping features and frequently pose a diagnostic challenge. We aim to highlight important clinical clues to facilitate distinguishing these syndromes and aid in appropriate management.