Study Design Systematic review and meta-analysis. Background An increasing number of physical therapists in the United States and throughout the world are using dry needling to treat musculoskeletal pain. Objective To examine the short- and long-term effectiveness of dry needling delivered by a physical therapist for any musculoskeletal pain condition. Methods Electronic databases were searched. Eligible randomized controlled trials included those with human subjects who had musculoskeletal conditions that were treated with dry needling performed by a physical therapist, compared with a control or other intervention. The overall quality of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation. Results The initial search returned 218 articles. After screening, 13 were included. Physiotherapy Evidence Database quality scale scores ranged from 4 to 9 (out of a maximum score of 10), with a median score of 7. Eight meta-analyses were performed. In the immediate to 12-week follow-up period, studies provided evidence that dry needling may decrease pain and increase pressure pain threshold when compared to control/sham or other treatment. At 6 to 12 months, dry needling was favored for decreasing pain, but the treatment effect was not statistically significant. Dry needling, when compared to control/sham treatment, provides a statistically significant effect on functional outcomes, but not when compared to other treatments. Conclusion Very low-quality to moderate-quality evidence suggests that dry needling performed by physical therapists is more effective than no treatment, sham dry needling, and other treatments for reducing pain and improving pressure pain threshold in patients presenting with musculoskeletal pain in the immediate to 12-week follow-up period. Low-quality evidence suggests superior outcomes with dry needling for functional outcomes when compared to no treatment or sham needling. However, no difference in functional outcomes exists when compared to other physical therapy treatments. Evidence of long-term benefit of dry needling is currently lacking. Level of Evidence Therapy, level 1a. J Orthop Sports Phys Ther 2017;47(3):133-149. Epub 3 Feb 2017. doi:10.2519/jospt.2017.7096.