Abstract | Sudden infant death syndrome (SIDS) is the leading cause of post-neonatal infant mortality in developed countries, characterized by the death of infants for no obvious reason and without prior warning. The complex interaction of multiple factors in the pathogenesis of SIDS is illustrated by the ‘triple risk hypothesis', which proposed that SIDS results from a convergence of three overlapping risk factors: a critical developmental period, an exogenous stressor, and underlying genetic and/or nongenetic vulnerability in the infant. Rare variants in genes associated with inherited arrhythmia syndromes and cardiomyopathies have been proposed as the substrate for an infant's critical vulnerability in a small subset of SIDS cases. Given the potential risk of inherited cardiac disease, current guidelines recommend post-mortem genetic testing (molecular autopsy) and cardiological investigation of the surviving family, complemented by targeted genetic testing if appropriate. In this Review, we highlight the latest developments in understanding the spectrum and prevalence of cardiac-mediated SIDS, and discuss the clinical implications of SIDS in the surviving family and the general population.