<p>The authors of both national and international sepsis guidelines leave it up to clinician discretion whether hydrocortisone should be supplemented with fludrocortisone in cases of septic shock. The aim of this review is to present and discuss the available evidence and the rationale behind the combination of hydrocortisone and fludrocortisone as compared to hydrocortisone alone or standard care for septic shock. In addition to presenting new results from clinical trials and meta-analyses, arguments for and against the additive use of fludrocortisone are discussed and the underlying pathophysiological mechanisms are elucidated. Finally, clinically relevant guidance regarding the practical application of steroids in sepsis is provided.</p>