Sufficient analgesia, sedation, and paralysis, if necessary, are cornerstones of extracorporeal membrane oxygenation (ECMO) treatment protocols. However, increased distribution volumes, drug absorption by circuit materials, and impaired drug elimination, as well as alternations of cerebral perfusion and blood brain barrier function, result in the markedly altered pharmacodynamics of applied drugs. Today, narcotics combined with benzodiazepines, sometimes enforced by barbiturates, are commonly used in clinical practice. Paralysis is usually achieved by pancuronium or vecuronium. Although these drugs are used widely, actual efficacy remains uncertain because of the lack of reliable tools to measure pain relief and degree of sedation during ECMO, especially during paralysis. Taking into account the detrimental effects of insufficient pain relief and inadequate sedation in such unstable patients as children during pediatric cardiac ECMO, further studies on this topic seem urgently necessary.