Depression is the most common psychiatric disorder in primary care patients and is found in about 12.5% of patients, though depression is diagnosed much more often in patients with chro­nic medical conditions. The association between depression and chronic diseases appears to be mediated by some genetic and behavioural mechanisms, chronic stress and elevated concentration of pro-inflammatory cytokines in the central nervous system. Some of the pro-inflammatory cytokines in brain tissue activate different neuroendocrine and immune responses called “sickness behaviour”. In patients with rheumatoid arthritis (RA), depressive disorder occurs in 13–65% of cases, but only 25% of patients receive appropriate intervention. The high incidence of depression in RA patients is mainly caused by high levels of cytokines. Depression negatively impacts the course of rheumatoid arthritis and may even aggravate its somatic features. On the other hand, the results of treatment of depression appear to be worse in patients with rheumatoid arthritis and high disease activity, what decreases the efficacy of supportive therapy and increases the recurrences of depression after the first episode. Early diagnosis and treatment of depression related to rheumatoid arthritis should be an integral part of the management in rheumatoid arthritis and appropriate therapy of both conditions should be undertaken simultaneously. Depression can be difficult to recognize because many symptoms (for example fatigue, loss of appetite, loss of bodyweight, pain) can mimic those of rheumatoid arthritis. Even if depression is undiagnosed, it can still decrease the efficacy of the therapy for rheumatoid arthritis because of reduced patient’s compliance and involvement in treatment decisions. This may also increase suicidal ideation and attempts, and is linked to increased mortality in RA patients.