This systematic review analyses the efficacy, tolerability and safety of combinations of different medicines used to treat dyslipidemias in clinical practice. A PubMed search up to January 2009, was conducted to identify relevant studies. Criteria used to identify studies included (1) English language, (2) published studies with original data or meta-analyses in peer-reviewed journals. Although statin treatment is a mainstay of dyslipidemia management today, complementary effects of other lipid-lowering and/or HDL-cholesterol-raising therapies might substantially increase the clinical benefits not only in the small minority of patients with severe dyslipidemias but in others as well. These therapies include combinations with bile acid sequestrants (cholestyramine, colestipol, colesevelam), ezetimibe, niacin, plant sterols, fibrates (fenofibrate, bezafibrate, gemfibrozil), and prescription omega-3 fatty acids. Therapeutic approaches which incorporate the use of multiple drugs combinations for dyslipidemia treatment should be more widely adopted since combination therapy might offer a means to increase the number of patients able to meet their lipoprotein goals according to the guidelines. However, it has to be stated that for most of these combination therapies data on cardiovascular outcomes are still lacking.