The aim of this article is to review the literature regarding the relationship between vitamin D deficiency and cardiovascular disease (CVD) and its modification in the presence of obesity. Despite the strong association between vitamin D status and cardiovascular outcomes, vitamin D supplementation trials in the general population have failed to decrease the incidence of cardiovascular events and mortality. A comprehensive study of the published literature and a comparison with experimental data lead to the conclusion that obesity, due to its high prevalence and strong association with both vitamin D deficiency and CVD, may act as a critical confounder, which is responsible for the different results on this association. Adoption of a vitamin D preventive supplementation strategy for CVD is unlikely to yield any benefit to the general population. However, it might be particularly useful in obese adults with increased risk for CVD.