Vitamin D is a key nutrient for both healthy children and those with chronic illnesses. Understanding its roles in health and disease has become one of the most important issues in the nutritional management of children. Formal guidelines related to nutrient requirements for vitamin D in healthy children, recommending dietary intakes of 400 IU per day for infants and 600 IU per day for children over 1 year of age, were released by the Institute of Medicine in November 2010. However, application of these guidelines to children with acute and chronic illnesses is less clear. In this Review, we consider major illness categories and specific examples of conditions in children that might be affected by vitamin D. This information can be used in developing both model systems of investigation and clinical trials of vitamin D in children with acute and chronic illnesses.