The concept of a metabolic syndrome (MetS), a cluster of pre-clinical metabolic alterations commonly associated with obesity, is the object of much debate. Genetic studies have the potential to contribute to some of the key questions, including the true nature of the cluster of pre-clinical features and whether it is associated with human genetic variation. This review summarizes the evidence for the presence of familial aggregation for the individual components of MetS and their heritability levels. It also provides an overview of the studies that have dealt with candidate genes for MetS. Potential leads from genome-wide linkage scans are also discussed. The assumption is made that obesity, ectopic fat deposition and abnormal adipose tissue metabolism are responsible for alterations in lipid metabolism, which in turn generates the commonly observed pre-clinical shifts in glucose tolerance, lipids and lipoprotein profile, blood pressure, inflammatory markers, endothelial function, and a prothrombotic state. Progress in the understanding of the genetic basis of MetS should occur as soon as a consensus is reached on the true nature of MetS, its components and diagnostic criteria.