Medical nutrition therapy in critically ill patients remains challenging, not only because of the pronounced stress response with a higher risk for complications, but also due to their heterogeneity evolving from different phases of illness. The present review aims to address current knowledge and guidelines in order to summarize how they can be best implemented into daily clinical practice. Further studies are urgently needed to answer such important questions as best timing, route, dose, and composition of medical nutrition therapy for critically ill patients and to determine how to assess and to adapt to patients’ individual needs.