This review discusses the physiological role of vitamin D in disease prevention. Vitamin D is essential for human health and influences various physiological processes. It is hydroxylated in the liver and kidney to form calcifediol (25(OH)D) and calcitriol (1,25(OH)2D), which regulate calcium and phosphorus metabolism. Beyond its classical roles, vitamin D has been shown to impact the prevention and reduction of conditions such as cardiovascular diseases, autoimmune disorders, infections, and cancer. Vitamin D is obtained through sunlight, diet, and supplements, and its deficiency can lead to inflammation, oxidative stress, and increased susceptibility to metabolic disorders and infections. Maintaining serum 25(OH)D levels above 40 ng/mL is crucial for health and disease prevention. However, current recommended daily intake and serum 25(OH)D concentrations are outdated, preventing people from benefiting. Evidence suggests that maintaining 25(OH)D concentrations between 40–80 ng/mL is optimal for disease prevention and reducing morbidities and mortality without adverse effects. The review highlights the importance of vitamin D in immune function, bone health, and various physiological processes. It also discusses the challenges in maintaining adequate vitamin D levels due to insufficient sunlight exposure, dietary intake, and medication interactions. The review emphasizes the need for higher vitamin D intake to achieve optimal clinical outcomes and the importance of integrating vitamin D assessment and supplementation into clinical practice to improve health outcomes and reduce healthcare costs. The review also discusses the physiological functions of vitamin D, including its role in calcium homeostasis, immune function, and the regulation of various physiological processes. The review concludes that vitamin D is a crucial regulator of calcium homeostasis and has a broad positive impact on human health with minimal cost and little adverse effects.This review discusses the physiological role of vitamin D in disease prevention. Vitamin D is essential for human health and influences various physiological processes. It is hydroxylated in the liver and kidney to form calcifediol (25(OH)D) and calcitriol (1,25(OH)2D), which regulate calcium and phosphorus metabolism. Beyond its classical roles, vitamin D has been shown to impact the prevention and reduction of conditions such as cardiovascular diseases, autoimmune disorders, infections, and cancer. Vitamin D is obtained through sunlight, diet, and supplements, and its deficiency can lead to inflammation, oxidative stress, and increased susceptibility to metabolic disorders and infections. Maintaining serum 25(OH)D levels above 40 ng/mL is crucial for health and disease prevention. However, current recommended daily intake and serum 25(OH)D concentrations are outdated, preventing people from benefiting. Evidence suggests that maintaining 25(OH)D concentrations between 40–80 ng/mL is optimal for disease prevention and reducing morbidities and mortality without adverse effects. The review highlights the importance of vitamin D in immune function, bone health, and various physiological processes. It also discusses the challenges in maintaining adequate vitamin D levels due to insufficient sunlight exposure, dietary intake, and medication interactions. The review emphasizes the need for higher vitamin D intake to achieve optimal clinical outcomes and the importance of integrating vitamin D assessment and supplementation into clinical practice to improve health outcomes and reduce healthcare costs. The review also discusses the physiological functions of vitamin D, including its role in calcium homeostasis, immune function, and the regulation of various physiological processes. The review concludes that vitamin D is a crucial regulator of calcium homeostasis and has a broad positive impact on human health with minimal cost and little adverse effects.