Atypical facial pain, stomatodynia, atypical odontalgia, and some forms of masticatory muscle and temporomandibular joint disorders all seem to belong to the same group of idiopathic orofacial pain illnesses. The many common clinical features they display have been discussed in a preceding paper. Some of their common pathophysiologic mechanisms are reviewed in this article. The role of female hormones is suggested as a risk factor by the strong female prevalence and by the effects of physiologic and therapeutic modification of estrogen levels in patients with these pain conditions. Osteoporosis, which appears with menopause, and neuralgia-inducing cavitational osteonecrosis have been linked to atypical facial pain. Similar clinical features have also prompted a comparison between atypical facial pain and complex regional pain syndrome of the limbs. The presence of psychosocial factors is also a common feature, but it is not known whether these are causal or whether the pain induces the psychosocial problem. Local inflammatory, infectious, or mechanical irritation as well as minor nerve trauma are frequently reported in these conditions and can also be considered as risk factors. However, none of the above factors can currently be considered as the sole etiologic factor, and instead the following hypothesis is proposed: the idiopathic pain entities depend on one or several neuropathic mechanisms, the development of which is triggered or favored by one or several events or risk factors. Different neuropathic mechanisms may be at work: nociceptor sensitization, phenotypic changes and ectopic activity from the nociceptors, central sensitization possibly maintained by ongoing activity from initially damaged peripheral tissues, sympathetic abnormal activity, alteration of segmental inhibitory control, and hyper- or hypoactivity of descending controls. Research directions that are suggested include epidemiologic approaches to improve the clinical definition of these conditions, studies to test for the factors and mechanisms proposed, and definition of mechanism-based diagnostic and treatment strategies.