Cancer patients with advanced disease frequently feel weak and fatigued, and have an increased risk of fracture. At the same time several reports describe the high prevalence of vitamin D deficiency in these patients. This review will summarize the impact of vitamin D deficiency on muscle weakness and fracture risk. While larger clinical trials of vitamin D supplementation are lacking in cancer patients, the evidence from clinical trials among older adults of the general population support a significant benefit of vitamin D on muscle strength, and fall and fracture reduction. Mechanistic evidence regarding the presence of the specific vitamin D receptor in muscle tissue and muscle biopsy abnormalities observed with deficiency will be reviewed, as well as molecular and non-molecular effects of vitamin D in muscle tissue. At the clinical level, the evidence from randomized controlled trials of vitamin D supplementation on functional improvement and fall reduction will be summarized. Finally, trial and epidemiological data will be reviewed to assess desirable serum 25-hydroxyvitamin D levels for optimal muscle health.