Skeletal muscle relaxants are widely used in treating musculoskeletal conditions. However, evidence of their effectiveness consists mainly of studies with poor methodologic design. In addition, these drugs have not been proven to be superior to acetaminophen or nonsteroidal anti-inflammatory drugs for low back pain. Systematic reviews and meta-analyses support using skeletal muscle relaxants for short-term relief of acute low back pain when nonsteroidal anti-inflammatory drugs or acetaminophen are not effective or tolerated. Comparison studies have not shown one skeletal muscle relaxant to be superior to another. Cyclobenzaprine is the most heavily studied and has been shown to be effective for various musculoskeletal conditions. The sedative properties of tizanidine and cyclobenzaprine may benefit patients with insomnia caused by severe muscle spasms. Methocarbamol and metaxalone are less sedating, although effectiveness evidence is limited. Adverse effects, particularly dizziness and drowsiness, are consistently reported with all skeletal muscle relaxants. The potential adverse effects should be communicated clearly to the patient. Because of limited comparable effectiveness data, choice of agent should be based on side-effect profile, patient preference, abuse potential, and possible drug interactions.