Vitamin B3, or niacin, is an essential water-soluble B-complex vitamin vital for DNA repair, energy production, and various metabolic processes. Its significance was highlighted in the context of Pellagra, a niacin-deficiency disorder characterized by diarrhea, dermatitis, dementia, and death. This chapter examines niacin’s digestion, metabolism, and dietary sources, including whole grains and proteins, while discussing its conversion from the amino acid tryptophan. Key metabolites, NAD and NADP, are emphasized for their roles in energy metabolism and oxidative processes. The chapter also addresses factors contributing to niacin deficiency, such as undernutrition and specific disorders, along with the clinical manifestations of Pellagra. Additionally, it covers potential toxicity associated with excessive niacin intake and its therapeutic applications in managing dyslipidemia and emerging roles in dermatological and neurological conditions. Through this chapter, the complex role of niacin in health and disease is elucidated.