Serum cortisol free fraction is responsible for its physiological function. Determination of serum total cortisol concentration does not allow accurate evaluation of hypothalamic pituitary adrenal axis when there is a quantitative variation in serum transcortin. Although free cortisol can be assayed by salivary or urinary cortisol measurements, these methods can not be easily applied in intensive care units. Free plasmatic cortisol measurement could provide a better reflect of circulating cortisol in patients with critical illness whom have a decreased concentration of binding proteins and whom adrenal status is an important prognostic factor. Free cortisol can be measured after separation from bound cortisol, calculated with equation based on equilibrium binding or evaluated by cortisol/CBG ratio. In various studies, free plasmatic cortisol allows in critical care patients a better appreciation of adrenal status than total cortisol and be more differential than total cortisol increment after stimulation with synacthen used to diagnose "relative adrenal insufficiency".