Introduction. Musculoskeletal disorders (MSDs) are the main reason for disability in the world, causing pain and functional loss. Class IV laser is a recent treatment proposed for pain reduction in MSDs, although studies supporting its use and dosage are limited. The purpose of the paper was to describe the efficacy of class IV laser in the treatment of musculoskeletal pain. Methods. Randomized clinical trials were identified in the PubMed, Scopus, Web of Science, CINAHL, and ScienceDirect databases by a search on August 31, 2020. Three independent investigators reviewed article titles and abstracts for eligibility. Risk of bias and quality were evaluated with the Cochrane risk of bias tool and PEDro scale. Decreased pain was considered the main outcome; range of motion, strength, or disability were secondary outcomes. Results. A total of 50 articles were obtained after eliminating duplicates, reduced to 7 after selection criteria application. MSDs included patellofemoral dysfunction (n = 1), epicondylitis (n = 1), osteoarthritis (n = 1), cervicalgia (n = 3), and lumbar radiculo pathy (n = 1). The studies had a low risk of bias and a PEDro score greater than 7. Pain reduction was observed at the end of laser treatments and in followup evaluations (p < 0.005); the decrease in disability favoured laser management (p < 0.005). Conclusions. Class IV laser is effective in reducing pain and improving function in patients with MSDs. Further research is necessary to establish a consensus on the dosage and obtain more evidence in MSDs of nonarticular origin.