Updated treatment recommendations for the therapy of rheumatoid arthritis (RA) in South Africa advocate early diagnosis, prompt initiation of disease-modifying anti-rheumatic drugs (DMARDs), and an intense treatment strategy where disease activity is assessed with a composite score such as the Simplified Disease Activity Index (SDAI). Frequent assessments and escalation of therapy are necessary until low disease activity (LDA) (SDAI ≤11) or ideally remission (SDAI ≤3.3) is achieved. Synthetic DMARDs may be used as monotherapy or in combination, and can be co-prescribed with low-dose corticosteroids if necessary. Biologic DMARD therapy should be considered for patients who have failed a 6-month trial of at least 3 synthetic DMARDs. All RA patients in SA are at increased risk of tuberculosis (TB), in particular patients using anti-tumour necrosis factor (TNF) biologic therapy. These recommendations provide practical suggestions for the screening and management of TB and other comorbidities, and offer an approach to monitoring of RA patients.