IL-3 (also known as multispecific hemopoietin) is naturally produced by both Th1 and Th2 lymphocytes, mast cells, and eosinophils. IL-3 stimulates the production of macrophages, granulocytes, and dendritic cells from bone marrow precursors. The IL-3 is involved in bone marrow hemopoiesis and dendritic cell maturation in anti-viral or antitumor reactivity. IL-3 binds with high affinity to the IL-3 receptor α (IL-3Rα/CD123) and then associates with the βc subunit. IL-3 is the most important growth and activating factor for human and mouse basophils, primary effector cells of allergic disorders. IL-3-activated basophils and mast cells are also involved in different chronic inflammatory disorders, infections, and several types of cancer. IL-3 induces the release of cytokines (i.e., IL-4, IL-13, CXCL8) from human basophils and preincubation of basophils with IL-3 potentiates the release of proinflammatory mediators and cytokines from IgE and C5a-activated basophils. IL-3 synergistically potentiates IL-33-induced mediator release from human basophils. IL-3 plays a pathogenic role in several hematologic cancers and may contribute to autoimmune and cardiac disorders.IL-3Rα/CD123 is also highly expressed on human plasmacytoid DCs, making IL-3 a crucial survival factor for the rare blastic plasmacytoid DC neoplasm (BPDCN). IL-3 supports the proliferation of mouse and human B cells. IL-3 and GM-CSF stimulate the adhesion of human monocytes to endothelial cells. Human endothelial cells are an important target of IL-3. IL-3 activates IL-3 receptor and the proliferation of human endothelial cells and promotes in vivo vessel formation. The proangiogenic activity of IL-3 could contribute to its role in cancer initiation and progression. IL-3 is a growth factor for microglia and modulates mouse and human neurons. Finally, IL-3 regulates bone homeostasis through the modulation of osteoblast differentiation.