The metabolic syndrome (MetS) is strongly associated with insulin resistance and consists of a constellation of factors that raise the risk for cardiovascular diseases and diabetes mellitus. Therefore, the primary goals of treating MetS are prevention of type 2 diabetes and cardiovascular events. Three levels of intervention may be considered for individuals with MetS : 1) management of underlying risk conditions by controlling weight excess, enhancing regular physical exercise and promoting healthy diet; 2) management of individual risk factors such as dyslipidaemia, hypertension, hyperglycaemia and prothrombotic state; and 3) targeting insulin resistance by using specific insulin sensitizers such as thiazolidinediones. The most important therapeutic intervention effective in subjects with MetS should focus on modest weight reduction and regular leisure-time physical activities. Although lifestyle modification is the first-line therapy, drug therapy may be necessary in many patients to achieve recommended goals regarding lipid profile, blood pressure and blood glucose control. Rather than to use a magic bullet that might fully reverse the underlying cause of the syndrome, one appealing alternative would be to use a so-called "polypill" targeting each of the components of MetS. However, such a polypill should ideally contain numerous molecules that all have shown a potential interest for the management of MetS such as metformin, acarbose, a thiazolidinedione, a statin, a fibrate, an inhibitor of the renin-angiotensin system, aspirin. The growing prevalence and high-risk nature of MetS highlights the need to identify individuals with this condition and to treat them with an aggressive multitargeted approach.