Muscle relaxants are commonly prescribed for low back pain (LBP); however, there is limited evidence of their clinical efficacy and tolerability. This review evaluated the efficacy and tolerability of muscle relaxants in people with LBP. We searched online databases including Medline, EMBASE, CENTRAL and PsycINFO (inception to end October 2015) and performed citation tracking for eligible randomized controlled trials (RCTs). Two authors independently extracted data and assessed risk of bias of randomized controlled trials of muscle relaxants. Pain outcomes were converted to a common 0–100 scale. Data were pooled using a random effects model with strength of evidence assessed using GRADE. Fifteen trials (3362 participants) were evaluated in this review. A total of five trials (496 participants) provide high quality evidence that muscle relaxants provide clinically significant pain relief in the short term for acute LBP; MD −21.3, [−29.0, −13.5]. There was no information on long-term outcomes. The median adverse event rate in clinical trials for muscle relaxants was similar to placebo 14.1% IQR (7.0–28.7%) and 16.0% (4.1–31.2%); p = 0.5, respectively. There is no evidence for the efficacy of benzodiazepines in LBP. For people with acute LBP, muscle relaxants provide clinically significant short-term pain relief. For chronic LBP, the efficacy of muscle relaxants is largely unknown. There was no eligible RCT evidence to support the efficacy of benzodiazepines in LBP. Prolonged use of these medicines in LBP cannot be guided by trial evidence. What does this review add?: Muscle relaxants provide clinically significant pain relief for acute low back pain. Caution must be taken with the interpretation of the findings as the evidence comes from specific muscle relaxant medicines.