Patients with various rheumatologic and inflammatory disease states commonly require drugs known to decrease the inflammatory or autoimmune response for adequate control of their condition. Such drugs include nonsteroidal antiinflammatory drugs (NSAIDs), cyclooxygenase (COX)-2 inhibitors, corticosteroids, disease-modifying antirheumatic drugs (DMARDs), and biologic response modifiers. These drugs affect inflammation and local immune responses, which are necessary for proper wound healing in the perioperative setting, thereby potentially resulting in undesirable postoperative complications. Such complications include wound dehiscence, infection, and impaired collagen synthesis. The end result is delayed healing of soft tissue and bone wounds. The current literature provides insight into the effect of some of these drugs on wound healing. For certain drugs, such as methotrexate, trials have been conducted in humans and direct us on what to do during the perioperative period. Whereas with other drugs, we must rely on either small-animal studies or extrapolation of data from human studies that did not specifically look at wound healing. Unfortunately, no clear consensus exists on the need and optimum time for withholding therapy before surgery. Likewise, clinicians are often uncertain of the appropriate time to resume therapy after the procedure. For those drugs with limited or no data in this setting, the use of pharmacokinetic properties and biologic effects of each drug should be considered individually. In some cases, discontinuation of therapy may be required up to 4 weeks before surgery because of the long half-lives of the drugs. In doing so, patients may experience an exacerbation or worsening of disease. Clinicians must carefully evaluate individual patient risk factors, disease severity, and the pharmacokinetics of available therapies when weighing the risks and benefits of discontinuing therapy in the perioperative setting.