Cardiovascular disease (CVD) is the most common cause of death in Western countries and will continue to be so in upcoming years. A close correlation has been demonstrated among CVD, stroke, ischemic heart disease, renal failure and a number of modifiable risk factors. As cardiovascular (CV) risk factors commonly co-exist, high-risk patients with hypertension, obesity and diabetes may well benefit from a multiple action combination of CV agents with synergistic efficacy. Control of blood pressure (BP) and the other CV risk factors is still far from the optimal rates and achievement of internationally accepted goals must be imperative. The benefits of achieving these goals, including significant reductions in CV morbidity and mortality, are well documented. Thus, a rigorous effort to improve BP goal attainment is required. Most of the patients will need two or more antihypertensives to achieve BP goal. Administering of two drugs in a single-dose formulation substantially improves patient compliance compared with separate agent administration. Fixed-dose combination therapy can offer potential advantages over individual agents, including increased efficacy, reduced incidence of adverse effects, lower healthcare costs and improved patient compliance through the use of a single medication administered once daily. Currently available fixed-dose agents include several combinations with complementary pharmacodynamic activity. Last, the polypill includes several CV acting agents that affects various CV risk factors and offers encouraging results, although more data are needed to strengthen the polypill concept, its efficacy and safety.