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The past decade has seen a major change in the treatment options and strategies for rheumatoid arthritis (RA) and the other immune-mediated arthritic diseases. The disease modifying antirheumatic drugs (DMARDs) are now used in early stages of the disease in order to preserve joint architecture. There are two groups of DMARDs, the small molecules, like methotrexate, and the biological DMARDs, which are frequently referred to as “magic bullets” since they target specific cytokines and immune cells associated with arthritic conditions. They are monoclonal antibodies or fusion proteins designed to bind and inactivate immune targets. Tumour necrosis factor-alpha (TNF-α) plays an important role in the pathogenesis of rheumatoid disorders and is the target of four biological DMARDs, etanercept, infliximab, golimumab and adalimumab. The other biological DMARDs include abatacept, rituximab and tocilizumab and these prevent T-cell costimulation, cause the depletion of mature CD20 positive B cells or prevent the activation of the interleukin-6 receptor molecule, respectively. Ustekinumab, a monoclonal antibody against IL12/IL23 is effective in psoriatic arthritis. Biological agents are indicated when patients do not respond adequately to the traditional DMARDs. Numerous clinical trials have shown that the biological agents reduce joint inflammation and erosive damage, especially when used in combination with methotrexate. Apart from their prohibitive cost, the biological agents are not without potentially serious adverse effects with infections being the main concern. The TNF-α inhibitors increase the risk for tuberculosis and other opportunistic infections, whereas the non-TNF-α immune inhibitors increase the risk for opportunistic viral, fungal and bacterial infections. This review provides an overview of the biological agents currently available in South Africa.