Over the past decade, remarkable progress has been made in the study of molecular mechanisms involved in degenerative temporomandibular joint arthritides. Based on recent findings, models of degenerative temporomandibular joint disease predict that mechanical loads trigger a cascade of molecular events leading to disease in susceptible individuals. These events involve the production or release of free radicals, cytokines, fatty acid catabolites, neuropeptides, and matrix-degrading enzymes. Under normal circumstances, these molecules may be involved in the remodeling of articular tissues in response to changing functional demands. However, if functional demands exceed the adaptive capacity of the temporomandibular joint or if the affected individual is susceptible to maladaptive responses, then a disease state will ensue. An individual's susceptibility to degenerative temporomandibular joint disease may be determined by several factors, including genetic backdrop, sex, age, and nutritional status. It is hoped that, by furthering our understanding of the molecular events that underlie degenerative temporomandibular joint diseases, improved diagnostics and effective therapies for these debilitating conditions will be developed.