Diacutaneous Fibrolysis (DF) is an instrumentally assisted manual therapy technique defined as “a specific instrumental intervention for normalizing the musculoskeletal system function after a precise diagnosis and preserving the skin’s integrity”. The aim of this technique is soft tissue mobilization with the assistance of specially designed, hook-shaped steel instruments in different musculoskeletal structures, such as the myofascia, aponeurosis, tendons, ligaments and scar tissues. Due to discrepant results between previous reviews and the quite abundant new evidence provided by recently published randomized clinical trials, we propound this narrative review to provide an update on the scientific evidence related to the fundamentals and clinical efficacy of DF. Current evidence primarily supports the mechanical effect of DF on connective soft tissues. Diminished deep tendon reflex and rigidity have been registered after the implementation of DF in healthy subjects. Though there is still much to uncover, scientific evidence supports the use of the technique for the clinical treatment of subacromial impingement syndrome, chronic lateral epicondylalgia, chronic patellofemoral pain syndrome, mild to moderate carpal tunnel syndrome, hamstring shortening, temporomandibular disorders, tension-type headache and chronic low back pain. Additional data are essential for better recommendations in the clinical practice of DF.