Replacement with adrenal steroids comprises treatment with glucocorticoids, mineralocorticoids and adrenal androgen precursors, mainly in patients with adrenal insufficiency. Attention has also been directed to replacement treatment with glucocorticoids in critically ill patients or with dehydroepiandrosterone (DHEA) in elderly people with an age related decline of DHEA/DHEAS levels. Despite the use of current replacement concepts well-being is often not fully restored in patients with adrenal insufficiency. Innovations comprise the development of new delayed release glucocorticoid preparations that allow to better mimic the circadian cortisol secretion and may have the potential to improve the treatment of patients with adrenal insufficiency. Recent results from the CORTICUS study have not confirmed previous beneficial results and have led to restrictions in the use of hydrocortisone substitution therapy in patients with septic shock. Treatment with the androgen precursor DHEA in patients with adrenal insufficiency may improve quality of life. However, in patients with an age related decline of DHEA levels, the available evidence does not support the use of DHEA replacement as an anti aging treatment.