Opinions about the effect of vitamin D on risk of cardiovascular disease have changed substantially over the last half century. During the 1950s and 1970s, the dominant view was that vitamin D was a cause of cardiovascular disease. During the 1980s and 1990s, an increasing number of studies showed benefits from vitamin D, challenging earlier opinions that vitamin D was harmful. During the first decade of this century, the weight of scientific opinion has shifted 180° from that of 50 years ago, and the prevailing focus of research is on identifying the potential beneficial effects of vitamin D against cardiovascular disease. Since 2003, large epidemiological studies of hemodialysis patients and general population samples have shown inverse associations between vitamin D and cardiovascular disease. A growing body of laboratory and clinical research has identified several possible mechanisms to explain this association. These include adverse effects of vitamin D deficiency on immune and inflammatory processes, endothelial function, matrix-metalloproteinases and insulin resistance, which result in cardiac hypertrophy, thickened arteries, increased plaque formation, and rupture and thrombosis. Large randomized trials are required to determine with certainty whether vitamin D protects against cardiovascular disease.