The metabolic syndrome (MetS) is a commonly encountered cluster of clinical phenotypes, including central obesity, hypertension, hyperglycemia, and dyslipidemia. Identifying genetic determinants of MetS will lead to better understanding of its progression and pathogenesis. To further the knowledge of MetS it is important to not only study the candidate genes for each individual component but to also investigate patients with rare monogenic disorders who express a cluster of the phenotypes commonly observed in MetS, however defined. In addition, certain genetic variants have been observed to increase or decrease the risk of developing the entire syndrome. It is apparent that only through complete understanding of the gene-gene, gene-gender and gene-nutrition interactions underlying MetS, will it become possible to determine or minimize the principal complications, namely type 2 diabetes and cardiovascular disease. In this review, we focus on the current evidence for common gene polymorphisms that predispose to or protect from the development of MetS.