Multiple factors impact fracture healing; thus, endocrine optimization and nutritional optimization warrant investigation in the acute fracture and nonunion patient. This article presents current evidence regarding the role of the endocrinologists and the dietician in the fracture patient as well as the most recent data assessing the vitamin D axis in these populations. Similarly, the most recent information regarding the use and risks of NSAIDs in fracture healing are presented. The fracture surgeon must consider each individual patient and weigh the benefits versus the costs of host optimization.