Vitamin D is known to play an essential role in calcium homeostasis; however, excessive amounts can have harmful effects. Calcium and vitamin D levels are known to be influenced by drug interactions and pathology ranging from cancer to cardiovascular disease. Vitamin D supplementation has become widespread, and it is important for clinicians to understand the way that certain conditions and medications interact with vitamin D and calcium homeostasis. The purpose of this review is to outline the benefits and adverse effects of vitamin D and how its levels are affected by certain pathologic and pharmacologic interactions.