The ability of the skin to serve as a protective shield against environmental challenges and as a sensitive detector and responder to thermal, chemical, and mechanical stimuli speaks to its exquisite design. A central feature of this design is the diverse array of neuronal afferents that convey and respond to sensory stimuli that the skin encounters. Cutaneous neuron development, form, and function are highly dependent on communication with the skin through its production of multiple growth factor proteins that modulate afferent development, maturation, and function. Production by the skin of neurotrophin growth factors and members of the glial cell line—derived neurotrophic factor family are particularly important for support of specific subsets of sensory neurons with unique phenotypic and functional properties. Although these proteins have central roles in afferent development and function, challenges remain in identifying specific molecular mechanisms of growth factor communication and understanding how activation of signaling pathways direct neuron differentiation and function under normal and pathological conditions. NEUROSCIENTIST 13(4):371—382, 2007. DOI: 10.1177/1073858407299425