The cellular processes that unfold in critical illness involve a variety of circulating substances, that may provide clinically relevant insight into the severity and outcome. Among hormonal markers, cortisol, several thyroid-related substances, as well as natriuretic peptides are discussed in this review. Glucose and lipids constitute metabolic markers, the identification and treatment of the former has been of particular importance. Among immune markers, both proinflammatory and anti-inflammatory cytokines, such as interleukin-6, contribute essential prognostic information. Finally, the complement and coagulation pathways also provide unique insight into this complex and heterogeneous process.