IL‐34 is a recently discovered cytokine that acts on tissue resident macrophages and Langerhans cells upon binding the receptor for CSF‐1, CSF‐1R. The existence of two ligands for CSF‐1R, IL‐34, and CSF‐1, raises several intriguing questions. Are IL‐34 and CSF‐1 redundant or does each perform temporally and spatially distinct functions? Is IL‐34 involved in human pathology? Would therapeutic strategies based on selective inhibition or administration of either IL‐34 or CSF‐1 be advantageous for preventing human pathology? Recent in vivo studies indicate that IL‐34 promotes the development, survival, and function of microglia and Langerhans cells; therefore, this cytokine may predominately function in brain and skin biology. Here, we review the evidence for IL‐34 as a key cytokine in the development and function of these two diverse cell types and discuss its potential role in pathological conditions.