Vitamins (e.g., vitamin A, B, C, D, and E) are organic compounds that are essential to maintaining health. Minerals, on the other hand, are inorganic substances that humans need to maintain their health (e.g., calcium, iron, zinc). Multivitamin and/or multimineral supplements contain three or more vitamins and/or minerals without herbs, hormones, or drugs. The U.S. Food and Nutrition Board of the Institute of Medicine has also determined that each of these components is present at a dose less than the tolerable upper intake level. We refer to multivitamin/multimineral supplements as multivitamins because this is how they are marketed and sold. We do not consider other essential nutrients, such as essential fatty acids, to be vitamins or minerals. Between 1941 and 1994, the Recommended Dietary Allowances (RDAs) of the United States and the Dietary Standards/Recommended Nutrient Intakes (RNIs) of Canada dictated the nutrition polices of their respective countries. By the 1990s, however, concerns about the accuracy of the RDAs and RNIs in both countries arose as nutritional research advanced and measurement of nutrients improved. In 1997, the Food and Nutrition Board published a broader set of dietary reference values called Dietary Reference Intakes (DRIs). DRIs expanded upon and replaced RDAs and RNIs with four categories of intakes intended to help individuals optimize their health, prevent disease, and avoid consuming too much of a specific nutrient. Most commercially available supplements generally contain vitamins and/or minerals at doses that are close to the recommended dietary allowance, but are still below the tolerable upper intake levels set by the U.S. Food and Nutrition Board. This systematic review was conducted to help the Agency for Healthcare Research and Quality (AHRQ) update its recommendation on the use of multivitamins for the prevention of cardiovascular disease (CVD) and cancer in the general population. The U.S. Preventive Services Task Force (USPSTF) will use this review to update its 2003 recommendations on routine vitamin supplementation to prevent chronic diseases. This review addresses the benefits and harms of single, paired, and multiple vitamins and/or minerals as primary prevention for CVD and cancer in the general population without nutritional deficiencies or existing chronic diseases.