Sepsis is a potentially fatal organ failure produced by the host's immune response to infection. It is critical to identify risk factors associated with a poor prognosis in septic patients in order to develop new therapy options. Vitamin D deficiency (25-hydroxyvitamin cholecalciferol < 20 ng/mL) is common in critical and septic patients. Serum vitamin D concentrations are associated with an increased incidence of mortality in critically ill adult patients. In critically ill patients, vitamin D supplementation (a very high vitamin D 3 or cholecalciferol loading dosage as a single bolus dose ranging from 400,000 to 540,000 IU) is feasible and safe. Some of the trials and their post-hoc analyses evaluating vitamin D supplementation in severely sick individuals, including septic patients, suggested possible benefits in mortality (reduced 28-day mortality in the range of 8.1%-17.5%), and other outcomes (reduction in hospital length in the range from 9 to 18 days, and decrease in duration of mechanical ventilation in the range from 5 to 10 days). Despite the fact that many studies support the provision of vitamin D to septic patients, there are still many studies that contradict this opinion, and there is still debate about the recommendation to use vitamin D in sepsis. A pragmatic clinical approach in severe sepsis could be supplementation of vitamin D if serum levels are diminished (< 30 ng/mL). It appears that a single ultrahigh dose of vitamin D 3 (cholecalciferol) could be administered to the septic patient via an enteral tube, followed by daily or monthly maintenance doses. Parenteral administration might be reserved for a subgroup of septic patients with gastrointestinal, hepatic, or renal dysfunction. Future clinical trials designed exclusively for septic patients are required to assess the potential advantages of vitamin D. Possible impacts of selective activators of vitamin D receptors, such as paricalcitol, should be elucidated in sepsis. This emphasizes the requirement for more study and confirmation of any potential beneficial effects of vitamin D in sepsis.