The mediating effect of acceptance and mindfulness in the relationship between pain, depression, and physical disability was examined in 55 rheumatoid arthritis patients. Results showed that the relationship between pain and depression was mediated by both nonreact and acceptance. By contrast, the relationship between pain and physical disability was mediated by acceptance but not by nonreact. This study provides evidences that the influence of these processes is different on depression and on physical disability. These findings support models that take both general measures of mindfulness and content-specific measures of acceptance into account when conceptualizing rheumatoid arthritis. Theoretical and clinical implications are discussed.