Genetic alterations affecting the JAK-STAT signaling pathway are linked to several malignancies and hematological disorders in humans. Despite being one of the most extensively studied pathways, there remain many gaps to fill. JAK-STAT components are widely conserved during evolution. Here, we review the known roles of the JAK-STAT pathway in Drosophila immunity: controlling the different steps of hematopoiesis, both under physiological conditions and in response to immune challenge, and contributing to antiviral responses. We then summarize what is currently known about JAK-STAT signaling in renewal of the adult intestine, under physiological conditions or in response to ingestion of pathogenic bacteria.