Osteoarthritis (OA) is becoming an increasingly common problem as the population ages. Nurse practitioners are often the first and sometimes the only health care providers for many patients with OA. Nonpharmacologic therapy is the cornerstone of OA management, with drug therapy added as needed. Acetaminophen is commonly recommended as first-line pharmacologic therapy, followed by nonsteroidal anti-inflammatory drugs, celecoxib, and other alternative therapies for patients in whom simple analgesics are ineffective or unable to be used. It is important for nurse practitioners to understand the indications, risks, and benefits of these therapies so that they may effectively manage patients with OA.