For the first time, this review article outlines the current knowledge on endothelial RNase1 and its role in function and dysfunction of the endothelium, thereby focusing on the intensive research from recent years: Uncovering the underlying mechanisms of RNase1 function and regulation in response to acute as well as long-term inflammation, the role of RNase1 in context of vascular, inflammatory and infectious diseases and the potential to develop novel therapeutic options to treat these pathologies against the background of RNase1 function in endothelial cells. This evidence concerns the gene RNASE1 and infectious disease.