B-group vitamins (B1, B2, B3, B5, B6, B7, B9, B12) are water-soluble micronutrients essential for energy metabolism, one-carbon metabolism, neurotransmitter synthesis, and redox homeostasis. This chapter provides a comprehensive clinical review of B-vitamin status across internal medicinegynaecology, and neurology. In obesity and diabetes, B-vitamin insufficiency frequently coexists with metabolic dysfunction, contributing to insulin resistance, endothelial dysfunction, and cardiovascular risk, with metformin, GLP-based therapies, and bariatric surgery further depleting B12 and folate. In female reproductive medicine, folate-mediated one-carbon metabolism modulates ovulation, implantation, and pregnancy outcomes, with additional specificities in polycystic ovary syndrome and sickle cell disease. Neurologically, B-vitamin deficiency remains an important reversible cause of encephalopathy, myelopathy, peripheral neuropathy, and cognitive decline, while vitamin B6 excess causes dose-dependent sensory neuropathy. In elderly patients, age-related physiological and socioeconomic changes increase deficiency risk, particularly for B12. The chapter emphasizes shared mechanisms of B-vitamin metabolism and deficiencies, including homocysteine regulation, outlines practical monitoring strategies using functional biomarkers, addresses drug-nutrient interactions, and provides evidence-based supplementation guidelines. A unified, precision-medicine approach integrating early recognition, appropriate laboratory evaluation, and targeted supplementation/therapy optimizes outcomes across disciplines.