In infectious diseases, interferon-gamma (IFN-gamma) is generally accepted as one of the most important inducers of antimicrobial and immunoregulatory effects, and both seemingly contradictory effects, can be mediated by the same effector molecules. In detail, several IFN-gamma induced enzymes such as the inducible nitric oxide synthase (iNOS) as well as the indoleamine 2,3-dioxygenase (IDO) also exert this double function. In this review we focus on antimicrobial and immunoregulatory properties of both enzymes expressed by human endothelial cells, which are prominent players in infectious diseases, tumour immunology and transplant medicine.