Designing a therapeutic plan that involves the least risk of toxicity and the greatest chance of success is the goal of the modern physician. To better achieve this goal an understanding of the genetic basis for drug efficacy and toxicity is essential. Here we review the available information on the pharmacogenetics of drugs commonly used to treat rheumatic diseases in the hope that the application of this information to the patient will contribute to more effective and safer therapies for rheumatoid arthritis, systemic lupus erythematosus, and other inflammatory diseases.