To date there is scant literature addressing the pharmacological principles guiding glucocorticoid administration in ARDS. This review addresses how the administration mode plays a more significant role in affecting response than the specific molecule. Dosage (initial, overtime, and adjustments based on response), timing of initiation, mode of administration, duration of therapy, tapering, and co-interventions to support the glucocorticoid receptor α function are all essential elements to achieving optimal response to therapy.