The metabolic syndrome (MetS) concept gathers in a single entity a set of metabolic abnormalities that have in common a close relationship with ectopic deposit of lipids, insulin resistance, and chronic low-grade inflammation. It is a valuable teaching tool to help health professionals to understand and integrate the consequences of lipotoxicity and the adverse metabolic consequences of insulin resistance. Also, it is useful to identify subjects with a high risk for having incident type 2 diabetes. Systems biology studies have gained a prominent role in understanding the interaction between adipose tissue dysfunction, insulin action, and the MetS traits and co-morbidities (that is, non-alcoholic steatohepatitis, or NASH). This approach may allow the identification of new therapeutic targets (that is, de novo lipogenesis inhibitors for NASH). Treatment targets on MetS are the adoption of a healthy lifestyle, weight loss, and the control of the co-morbidities (hyperglycemia, dyslipidemia, arterial hypertension, among others). The long-term goals are the prevention of type 2 diabetes, cardiovascular events, and other MetS-related outcomes. In the last few decades, new drugs derived from the identification of innovative treatment targets have come on the market. These drugs have positive effects on more than one MetS component (that is, hyperglycemia and weight control). New potential treatment targets are under study.