Background: Interferential current is one of the most common electrotherapeutic modalities used in the treatment of painful conditions. Patients seeking medical help to reduce their musculoskeletal pain can be treated using interferential current. Objective: The current review aimed to analyze the recently available information regarding the efficacy of interferential current in alleviating the pain of musculoskeletal origin. Methods: This study used Scopus, CINAHL, Cochrane Library, Web of Science, MEDLINE, Embase, and EBSCOas as data sources. The initial selection of the studies, thorough assessment of the full articles, and extraction of the necessary study characteristics were carried out by two independent reviewers. Another two independent reviewers assessed the methodological quality of each included trial against 39 criteria. These criteria were integrated from several popular scales. Pain intensity-measured using the visual analog scale, numeric pain rating scale, or McGill Pain Questionnaire-was the outcome of interest. Results: This review included 35 trials of variable methodological quality from which 19 trials were selected for the meta-analysis. In general, interferential current alone versus placebo demonstrated a significant pain-relieving effect. On the other hand, interferential current showed no significant difference when added to standard treatment compared with placebo plus standard treatment or standard treatment alone. Similarly, interferential current showed no significant difference when compared with other single interventions (laser, transcutaneous electrical nerve stimulation, cryotherapy). Conclusions: Interferential current alone is better than placebo at discharge. However, the low number of studies raises suspicions about this conclusion. Interferential current alone or added to other interventions is not more effective than comparative treatments in relieving musculoskeletal pain.