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Skeletal muscle relaxants are frequently prescribed for low back pain and other musculoskeletal pain with or after failure of first-line treatments such as nonsteroidal anti-inflammatory drugs (NSAIDs). While there can be benefits of using skeletal muscle relaxants in the short term, the long-term effects are unclear. These medications are heterogeneous and not chemically related and have several important adverse effects that should be considered given their widespread utilization. In the United States, carisoprodol, chlorzoxazone, cyclobenzaprine, metaxalone, methocarbamol, and orphenadrine are FDA approved for acute musculoskeletal conditions. Baclofen, tizanidine, and dantrolene are approved for spasticity. There is no clear evidence to show superiority of one muscle relaxant over another in managing acute low back pain, and most studies only evaluate results at 12 weeks or less. Most guidelines and current evidence support short-term use for all medications discussed in this chapter.