This paper presents a comprehensive review of research relating psychological domains with response to therapy in patients with rheumatoid arthritis. A holistic approach to the disease was adopted by incorporating not only disease activity but also dimensions of the impact of disease on patients' lives. Psychological distress, including depression and anxiety, is common among patients with rheumatoid arthritis and has a significant negative impact on response to therapy and on patients' abilities to cope with chronic illness. Evidence regarding the influence of positive psychological dimensions such as acceptance, optimism, and adaptive coping strategies is scarce. The mechanisms involved in these interactions are incompletely understood, although changes in neuro-endocrine-immune pathways, which are common to depression and rheumatoid arthritis, seem to play a central role. Indirect psychological influences on therapeutic efficacy and long-term effectiveness include a myriad of factors such as adherence, placebo effects, cognition, coping strategies, and family and social support. Data suggest that recognition and appropriate management of psychological distress may improve response to treatment and significantly reduce disease burden.