Although corticosteroids have been used for more than 30 years in the context of extracorporeal circulation, there is an ongoing debate about the benefits of their routine application. Methylprednisolone was given as early as 1966 to reduce vasoconstriction during cardiopulmonary bypass (CPB) and to prevent low output syndrome thereafter. An explanation for these findings was recently published. Lipid mediators lead to vasoconstriction and inflammatory cytokine production during CPB. There is no doubt about the potential of corticosteroids to reduce inflammatory and enhance anti-inflammatory mediators, while their possible influence on clinical parameters and their side effects are controversial, as discussed in the literature. There have been contradictory results with respect to pulmonary oxygenation, while an increase in the patient’s blood glucose levels, however clinically unimportant, could be demonstrated. The influence of other drugs affecting the inflammatory response has to be taken into account, leading to a patient-specific recommendation for the use of corticosteroids during operations requiring CPB.