Experimental studies indicate that the proinflammatory cytokines interleukin-1, interleukin-6, and tumor necrosis factor-alpha are important regulators of bone resorption and may play an important role in age- and estrogen deficiency-related bone loss. Although the observation of accelerated bone loss in patients with inflammatory disorders supports this mechanism, the role of cytokines in the etiology of osteoporosis has yet to be determined. Elucidation of this potential relationship could not only provide clinicians with an additional tool to identify patients at risk for osteoporosis, but may also inform the development of cytokine-blocking therapies as potential interventions to curb bone loss. Although some epidemiologic studies suggest increases in proinflammatory cytokines are associated with decreased bone mass and greater fracture risk, the totality of evidence is limited and provides no clear indication of which cytokines may be most important for bone health. Additional studies are required to establish if inflammation is an important risk factor for osteoporosis.