The recent removal of refecoxib (a cyclo-oxygenase II inhibitor), a drug involved in a large prostate cancer chemoprevention trial, and the completion of recruitment for the SELECT cancer chemoprevention trial utilizing selenium and vitamin E should lead researchers to ponder a similar question in cancer chemoprevention. The question of "What agent should be utilized and what clinical trial should designed and conducted next for cancer chemoprevention?" Part I and II of this manuscript attempts to argue that statins or cholesterol-lowering drugs or heart healthy agents are the ideal next choice for a large chemoprevention trial for numerous reasons including: (1) Cardiovascular disease (CVD) has been the number one cause of death in men and women every year in the US since 1900; (2) CVD has been the number one cause of death in the major cancer chemoprevention trials; (3) CVD has been the number one or two cause of death of men and women postdiagnosis of breast, colorectal, and prostate cancer; and (4) the recent potential relationship between certain cancers and dyslipidemia needs to be investigated. What other chemoprevention agent can also boast that in the worst case scenario the number one cause of death in men and women would probably be reduced in this future cancer chemoprevention trial of statins?! The list continues to grow of cancer chemoprevention trials that will probably be either a complete hit or miss. In other words, they will or have reduced the disease of interest with virtually no potential role for reducing the number one cause of death in men and women. The time seems more than overdue for a statin and/or another cholesterol lowering or heart healthy cancer chemoprevention trial.