Statins are a group of small-molecule inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase. They are commonly used to lower cholesterol levels. Recently, the potential role of statins in the inhibition of cancer has been the subject of intensive studies. Human trials have not provided conclusive results on the protective effects of statins against different cancers. A promising strategy to inhibit cancer is to use different agents in combination. The combination regimens with agents targeting multiple oncogenic aberrations may produce synergy and result in enhanced anticarcinogenic effects. The enhanced efficacy of the combination can lower the dose required for each agent in the combination. This in turn may reduce unwanted side effects possibly caused by high-dose, single-agent administration. Statins have been studied in combination with various agents, such as nonsteroidal anti-inflammatory drugs, dietary compounds, and chemotherapeutic agents. This article reviews the evidence for the possible synergistic action of these combinations and the mechanisms involved.