It is increasingly clear that coexistent disease plays a pivotal role in RA outcome and that efforts aimed at specifically addressing these comorbidities need to be aggressively sought, investigated, and implemented once proven effective. RA-associated costs are currently increasing at twice the rate of the medical care index. Comorbidity in the setting of RA independently predicts disease-associated disability (a major cost component) and mortality, underscoring the need for a more comprehensive approach to RA, one that adequately addresses disease-specific comorbidities. At present, many primary and secondary preventative measures (Table 1) for RA-specific comorbidities remain largely unproved and require rigorous investigation in a randomized prospective fashion. Despite this ongoing need, advances are being made in our understanding of the underlying pathogenesis of these comorbid conditions and their relation with RA. This improved understanding should translate into further effective interventions. Bisphosphonates, for instance, have been shown to be effective in the prevention of GIOP and associated fractures. The past several years have seen other exciting therapeutic advances in RA. DMARD combinations have been shown to be more effective and no more toxic than MTX monotherapy. In addition to the recent release of COX-2 NSAIDs, three new disease-modifying agents (leflunomide, etanercept, and infliximab) have been added to the therapeutic armamentarium; these are options that have markedly changed the treatment landscape in RA. Although these important advances have generated much deserved optimism, the precise effect that these agents may have on RA-specific comorbidity remains to be seen. The next decade should prove to be an exciting time in RA management. Better identification, understanding, and management of RA comorbidities have great potential to improve quality of life and survival among our patients with RA.