The human proteome is estimated to consist of around 78,000 proteins, the majority of which are splice variants of the ~20,000 ‘master proteins’ encoded in the human genome. Blood plasma, the most widely used biological fluid for both discovery and investigation in patients, has a reported 10,546 species of protein (1). With this diversity of protein content it is unsurprising that, when confronted with a systemic insult such as sepsis, the concentrations of many proteins are perturbed. The question for critical care physicians and researchers is whether these pertubations are mechanistically important for the diseases we treat or are simply epiphenomena of critical illness syndromes, organ failure and our therapeutic interventions.