Critically ill patients developing severe forms multiple organ dysfunction syndrome (MODS) may not be adequately supported by pharmacologic management. In these complex cases, a single form of extracorporeal organ support (ECOS) may be required, but multiple organ support therapy (MOST) is currently seen as a feasible approach. Severe renal dysfunction is a typical syndrome requiring renal replacement therapy (RRT) in the context of MODS. After more than a decade of RRT application in various intensive care settings, ECOS are not anymore seen as extraordinary or particularly aggressive techniques in MODS patients. Nowadays, a significant increase in the use of extracorporeal membrane oxygenation and extracorporeal carbon dioxide removal is occurring. When renal and cardio-pulmonary ECOS are used together, a multidisciplinary approach is necessary to minimize negative interactions and unwanted adverse effects. In this editorial, we focus on the organ crosstalk between the native and artificial organs, including the advantages and disadvantages of organ support on multiorgan function. Much of current experience on MOST has been gained upon RRT connected to other organ support therapies. Overall, available literature has not definitely established the ideal timing of these interventions, and whether early implementation impacts organ recovery and optimizes resource utilization is still a matter of open debate: it is possible that future research will be devoted to identify patient groups that may benefit from short- and long-term multiple organ support. Video Journal Club "Cappuccino with Claudio Ronco" at https://www.karger.com/Journal/ArticleNews/490694?sponsor=52.