Beside many efforts to improve outcome, sepsis is still one of the most frequent causes of death in critically ill patients. It is the most common condition with high mortality in intensive care units. The complexity of the septic syndrome comprises immunological aspects -i.e. , sepsis induced immunosuppression -but is not restricted to this fact in modern concepts. So far, exact mechanisms and variables determining outcome and mortality stay unclear. Since there is no typical risk profile, early diagnosis and risk stratification remain difficult, which hinders rapid and effective treatment initiation. Due to the heterogeneous nature of sepsis, potential therapy options should be adapted to the individual. Biomarkers like C-reactive protein and procalcitonin are routinely used as complementary tools in clinical decision-making. Beyond the acute phase proteins, a wide bunch of promising substances and non-laboratory tools with potential diagnostic and prognostic value is under intensive investigation. So far, clinical decision just based on biomarker assessment is not yet feasible. However, biomarkers should be considered as a complementary approach. Core tip: Sepsis is a complex continuum of disturbed systems. Despite the presence of clinical consensus criteria, the early diagnosis especially in the perioperative setting is challenging. A magnitude of potential new biomarkers is tested for this purpose, but evidence is mounting that due to the complex nature of the syndrome, biomarkers are rather complementary tools for clinical decision making than "magic bullets". Moreover, biomarkers are also evaluated for therapy guidance, linking diagnostic results to an individual therapeutic regime. This review summarizes the developments in the biomarker field, aiming to provide an overview about current targets and their limitations.