Metabolic syndrome (MetS) is the commonly observed clustering of obesity, hypertension, dyslipidemia, and insulin resistance. The components of MetS occur together more often than expected by chance and display significant heritability. Investigations into monogenic diseases that model features of the common MetS have uncovered responsible genes. Genome-wide association studies (GWAS) of the components of the MetS have been enormously successful. Meta-analysis of public GWAS data and risk-score analysis are revealing the role of common single-nucleotide polymorphism genotypes in MetS pathophysiology. A pleotropic polygenic architecture underlies MetS, making it a fascinating complex trait. Research will continue to uncover how metabolic pathways interact to form the MetS and its subsequent risk for atherosclerosis and diabetes.Metabolic syndrome is a clustering of cardiovascular risk factors that leads to an increased risk for premature cardiovascular disease and increased susceptibility of developing type 2 diabetes mellitus. The syndrome represents a collection of multiple derangements that include elevated blood pressure, impaired glucose tolerance or insulin resistance, atherogenic dyslipidemia (i.e., high triglycerides, low highâ€density lipoprotein [HDL] cholesterol, and small lowâ€density lipoprotein [LDL] particles), proinflammatory and prothrombotic properties, and obesity, with a particular contribution of abdominal obesity.