The diagnostic approach and the clinical management of critically ill patients is challenging. The recognition of biomarkers related to in-hospital mortality is of importance for identification of patients at increased risk of death. Many prediction models assessing the severity of illness and likelihood of hospital survival were developed using logistic regression analyses. These models include several laboratory parameters, such as white blood cell counts, serum bilirubin, serum albumin, blood glucose, serum electrolytes and markers which reflect acid-base disturbances. Recently, several other biomarkers, including troponin, B-type natriuretic peptide (BNP), N-terminal proBNP, C-reactive protein, procalcitonin, cholesterol and coagulation related markers have emerged as clinically useful tools for risk stratification and mortality prediction of heterogeneous and more specific subgroups of critically ill patients. More investigations are required to verify whether risk stratification based on mortality-related biomarkers may translate into targeted treatment strategies to improve clinical outcome of the critical illness. Biomarkers which are related to in-hospital mortality are highlighted in the current review.