Several acute and chronic pain conditions in the face or mouth are very common, and some are unique to the orofacial region. However, the etiology and pathogenesis of most orofacial chronic pain conditions are unresolved, and they are difficult to diagnose and manage. This article provides a brief overview of the neural mechanisms underlying orofacial pain and then highlights recent findings indicating that nonneural cells, specifically satellite cells in the sensory ganglia and astroglia and microglia cells in the central nervous system, are important players in both acute and chronic inflammatory and neuropathic orofacial pain conditions and may offer new targets for management of these conditions.