Activation of the immune system plays a key role in various diseases like infections, autoimmune diseases and malignancies or in cases of allograft transplantation. Also in neurological and cardiovascular diseases, immunological processes are discussed. To find the causative factor of pathologies and appropriate therapy, early and sensitive monitoring of immunological changes in patients is important. With this perspective, cellular immune activation conveniently and sensitively can be monitored by measuring neopterin in human body fluids. Neopterin, 2-amino-4-hydroxy-6-(D-erythro-1',2',3'-trihydroxypropyl)-pteridine, belongs to the class of pteridines which biosynthetically is derived from guanosinetriphosphate. When guanosinetriphosphate cyclohydrolase I is activated, most cells like fibroblasts or endothelial cells of several species produce tetrahydrobiopterin and only scarce amounts of neopterin derivatives are formed. Elevated neopterin levels indicate endogenous formation of gamma interferon and monitoring of neopterin levels therefore allows the activation status of the cell-mediated immune system to be examined. Stressors such as some xenobiotics, disease states and physical changes and various types of infections cause an increase in neopterin concentrations in biological fluids such as serum and urine. Neopterin as a biomarker is biologically stable. Furthermore, it has also been reported to be a strong predictor of disease progression. In this review, neopterin as a biomarker will be evaluated under the light of recent literature knowledge.