Neopterin is well established as a reliable marker in HIV-1 infection. Neopterin concentrations measured in urine or serum indicate sensitively the course and progression of the disease as well as efficacy of anti-retroviral therapy. The main trigger for neopterin production is Th1-type cytokine interferon-gamma. During acute HIV-1 infection, enhanced formation of neopterin occurs already at a very early time point, before antibody seroconversion takes place. After this stage, neopterin concentrations in serum and urine closely correlate with virus load in the circulation of HIV-1-infected patients. Data provide evidence for an important role of immune activation and Th1-type cytokine interferon-gamma in the pathogenesis of HIV-1 infection. This review subsumes the importance of neopterin as a marker in HIV-1 infection. Further evidence is increasing, that neopterin derivatives might modulate immune response by interfering with the cellular redox balance, activating redox-sensitive transcription factors, or inducing apoptosis in specific cell types. The possible impact of neopterin derivatives and of other biochemical pathways induced by interferon-gamma such as indoleamine 2,3-dioxygenase in chronic diseases like HIV-1 infection is discussed.