Niacin is required for a host of critical redox and adenosine diphosphate-ribosylation reactions in metabolism. Niacin deficiency leads to the distinctive signs and symptoms of pellagra, but these can happen in an unpredictable progression and can be altered in patients with polymorphisms in any of the hundreds of niacin-dependent enzymes. The symptomatology of niacin deficiency is becoming a forgotten knowledge base, and niacin deficiency is likely underdiagnosed. Additionally, high levels of niacin and niacinamide have pharmacological effects distinct from their role as sources of vitamin B3, allowing a wide range of effects on processes such as blood flow and lipid metabolism, which can be used to treat or prevent a variety of disease processes.