Multivitamin and mineral supplementation has been evaluated for disease prevention, cognitive preservation, symptoms, functional performance and biological aging. This narrative review integrates major randomized trials with regional publications, observational studies and selected unpublished academic work. The Physicians’ Health Study II demonstrated an 8% relative reduction in total cancer incidence and a reduction in cataract. The COSMOS cognitive studies demonstrated benefits in global cognition and episodic memory; a subsequent randomized ancillary analysis demonstrated slower progression of two epigenetic aging clocks. Selected antioxidant combinations reduced gastric cancer incidence or mortality in high risk populations. The principal broad spectrum prevention trials did not require dietary inadequacy or biochemical deficiency for enrollment, so deficiency should not be imposed retrospectively as a prerequisite for considering their results. Evidence nevertheless remains outcome specific: major cardiovascular events, incident dementia and overall survival have not been consistently improved by broad spectrum multivitamins. Smaller trials support improvements in selected measures of fatigue, stress, task performance and illness burden, although some tested products also contained nonvitamin ingredients. Clinical decisions should match the patient, intended outcome, formulation, dose and duration to the evidence. Supplementation is a reasonable option for selected adults similar to trial participants, including those without documented deficiency; the evidence does not establish an obligation for every adult to take a multivitamin.