Insight into protein requirements of intensive care unit (ICU) patients is urgently needed, but at present, it is unrealistic to define protein requirements for different diagnostic groups of critical illness or at different stages of illness. No large randomized controlled trials have randomized protein delivery, adequately addressed energy intake, and evaluated relevant clinical outcomes. As a pragmatic approach, experimental studies have focused on protein requirements of heterogeneous ICU patients. Data are scarce and the absolute value of protein requirements therefore is an approximation. Experimental studies indicate a protein requirement of >1.2 g/kg protein, which is supported by several outcome-based observational studies. Protein intake levels of up to 2.0–2.5 g/kg appear to be safe. A higher level of personalized treatment, within 1.2 and 2.5 g/kg, must involve identification of patients with low muscle protein mass that might benefit most from adequate protein nutrition in the ICU.