Rheumatic and musculoskeletal diseases (RMDs) are common, with osteoarthritis (OA) being the most prevalent. RMDs, including OA, are associated with significant pain and functional limitations, as well as mortality rates up to 1.6-fold higher than in the general population. Most studies of OA and mortality have focused on knee and hip OA. Some, but not all, of these studies suggest an increased risk of death, however risks may differ by region. Reasons for discordant findings may be due to methodological considerations including definition of OA, study design, length of follow-up, and whether variables that can change and develop over time, such as measures of OA, body mass index (BMI) and comorbidities, were re-assessed during the follow-up period. Research has shown that the prognosis of OA is similar to that seen in rheumatoid arthritis (RA) patients, in many respects. In RA, disability and comorbidities are the most important predictors of mortality, although pain may be more prominent in the prognosis of OA mortality. The data suggest that addressing functional limitations and pain seen with OA could potentially reduce the increased mortality that has been observed in these individuals. Further study is needed concerning the potential excess mortality attributable to lower body OA, as well as associated disability, pain and comorbidities.