The metabolic syndrome is defined by the presence of at least three of five disorders: central obesity, hypertriglyceridemia, low HDL-C, hypertension, and fasting hyperglycemia. The mechanisms leading to the development of the metabolic syndrome are not completely understood. The metabolic syndrome is probably a consequence of complex interactions of the primary disease, the pharmacological properties of the drug (s) and a number of other variable and invariant risk factors. Metabolic side effects of drugs significantly contribute to the development of metabolic syndrome, thus creating new health problems, which directly affects the adherence and effectiveness of prescribed therapy. Among the drugs that cause metabolic side effects, the most significant metabolic influence is attributed to the drugs from the group of antipsychotics, but a less prominent, yet significant impact on the metabolic profile of the patient can also be found in certain drugs from the groups of antiepileptics, corticosteroids (glucocorticoids), protease inhibitors and antihypertensives (thiazide diuretics and betablockers). The frequency and intensity of metabolic side effects varies between groups of drugs, as well as between drugs within each of the risk groups. Whenever possible, it is recommended to choose a drug with a more favorable effect on metabolic status, especially in high-risk patients who have other drug-related predispositions which additionally increase the risk of developing the metabolic syndrome. In the absence of more effective treatment options, ie. when therapy with a particular drug is necessary and the benefit-risk ratio is acceptable, metabolic side effects are minimized by combining continuous monitoring of key metabolic parameters, adjusting drug dosage, changing lifestyle habits and ultimately introducing therapy to reduce the negative effects of pharmacotherapy on the patients metabolism and to prevent potential complications to the patient's health.