The main effect of the active vitamin D metabolite 1,25(OH)2D is to stimulate the absorption of calcium from the gut. The consequences of vitamin D deficiency are secondary hyperparathyroidism and bone loss, leading to osteoporosis and fractures, mineralization defects, which may lead to osteomalacia in the long term, and muscle weakness, causing falls and fractures. Vitamin D status is related to bone mineral density and bone turnover. Vitamin D supplementation may decrease bone turnover and increase bone mineral density. Several randomized placebo-controlled trials with vitamin D and calcium showed a significant decrease in fracture incidence. However, very high doses of vitamin D once per year may have adverse effects. When patients with osteoporosis are treated with a bisphosphonate, they should receive a vitamin D and calcium supplement unless the patient is vitamin D replete. These subjects are discussed in detail in this review. Finally, the knowledge gaps and research agenda are discussed.