Sepsis is one of the leading causes of death in intensive care medicine in western countries. A strong body of evidence has been accumulated indicating that immediate resuscitation and restoration of tissue perfusion as well as early antibiotic treatment could significantly decrease the mortality in these patients. The clinical definitions of sepsis are basically nonspecific, often resulting in the delay of the diagnosis. Therefore, identification of specific clinical biomarkers may accelerate the diagnosis and thus improve sepsis treatment. During the last decade, a variety of different molecules have been proposed as clinical biomarkers in sepsis, most of which are still in the experimental stage. However, some have found their way into clinical practice and have evolved as valuable tools for diagnosis, therapy monitoring, and outcome prediction. This review will summarize the currently most important biomarkers and will discuss their clinical relevance.