Vitamin D, a calciotropic hormone, is gaining attention for many aspects of health, particularly metabolic regulation. As societal trends towards increasing caloric intake become more prominent, the concern for diseases stemming from chronic inflammation grows. Excess caloric intake results in increased lipid and fatty acid storage in adipose tissue leading to adipocyte hypertrophy and hyperplasia. Adipocytes produce cytokines and adipose-related hormones and can promote a systematic chronic proinflammatory state with the development of the metabolic syndrome and increasing risk of cardiovascular disease. Proinflammatory cytokines can signal immunocytes to injure the pancreas and endothelium. This, in turn can result in a reduction in insulin secretion and increasing insulin resistance. Vitamin D may possess therapeutic potential for metabolism associated diseases, as a result of its role in metabolic regulation as result of its action on adipocytes and myocytes. Vitamin D inhibits adipocyte maturation and Differentiation, and reduces the production of proinflammatory cytokines and adipose-related hormones by adipocytes. The purpose of this review is to elucidate the current literature on the therapeutic potential of vitamin D repletion in the treatment and prevention of metabolic and cardiovascular diseases. Although associations exist between vitamin D insufficiency and obesity, diabetes, hyperlipidemia, cardiovascular and all-cause mortality, there have not been prospective trials that have demonstrated the benefit of vitamin D in alleviating manifestations of disease. Nevertheless, correction of vitamin D insufficiency would be expected to confer many health benefits. A greater understanding of the interaction of vitamin D with not only adipose tissue but other components of the human metabolic regulatory system, such as the hypothalamus, pancreas, and bone, may help tailor interventions including vitamin D supplementations that address cardiovascular disease and obesity.