Penicillamine has proved an effective second line agent in rheumatoid arthritis. Its use, however, is limited by its toxicity. Long term studies show that only between 30 and 40% of patients started on penicillamine are still taking the drug at 2 years. Toxicity is the chief reason for stopping treatment, the commonest adverse effects requiring cessation of therapy being proteinuria (10 to 13%), skin rashes (5 to 9%), gastrointestinal events (5%) and thrombocytopenia or leucopenia (2 to 5%). A number of autoimmune syndromes may rarely be induced by penicillamine. HLA-B8, Dr3 positive individuals and poor sulfoxidisers are at increased risk of developing toxicity. Meticulous supervision of penicillamine therapy is required to minimise toxicity.