Polypill has been a hot issue since it was first advanced in 2003. This new concept immediately spurred a worldwide discussion. Xuezhikang is a partially purified extract of fermented red yeast rice (Monascus purpureus). It is composed of 13 kinds of natural statins, unsaturated fatty acids, ergosterol, amino acids, flavonoids, alkaloid, trace element, and other substances, and thus could be regarded as a natural lipid-lowering polypill. Interestingly, Xuezhikang in the China Coronary Secondary Prevention Study trial lowered lipid levels less as compared with provastatin in the Cholesterol and Recurrent Events trial, but seemed to gain more benefit in reducing the cardiovascular events and the risk of death from cancer. In recent years, Xuezhikang has been further demonstrated to have additional health benefits and thus raised great interest. This article reviews the clinical benefits of Xuezhikang and the potential multicomponent synergetic mechanism. The authors hold that polypill is anticipated to be a more effective and feasible way to treat complicated diseases.