Knee osteoarthritis (OA) is a common and morbid condition. No disease-modifying therapies exist; hence the goals of current treatment are to palliate pain and to retain function. OA pain is significantly influenced by the placebo effect. Nonpharmacologic interventions are essential and have been shown to improve outcomes. Canes, unloading braces, and therapeutic heating/cooling may be valuable. Pharmacotherapy options include topical and oral nonsteroidal anti-inflammatory drugs, duloxetine, and periodic intra-articular glucocorticoids and hyaluronans. Opioids, intra-articular stem cells, and platelet-rich plasma are not recommended. Novel targets such as nerve growth factor are under investigation and may be approved soon for OA pain.