Shoulder pain is a common problem with an estimated prevalence of 4% to 26%. About 1% of adults aged over 45 years consult their GP with a new presentation of shoulder pain every year in the UK. The aetiology of shoulder pain is diverse and includes pathology originating from the neck, glenohumeral joint, acromioclavicular joint, rotator cuff, and other soft tissues around the shoulder girdle. The most common source of shoulder pain is the rotator cuff, accounting for over two-thirds of cases.We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of oral drug treatment, topical drug treatment, local injections, non-drug treatment, and surgical treatment? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).We found 71 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.In this systematic review we present information relating to the effectiveness and safety of the following interventions: acupuncture, arthroscopic subacromial decompression, autologous whole blood injection, corticosteroids (oral, subacromial injection, or intra-articular injection), electrical stimulation, excision of distal clavicle, extracorporeal shock wave therapy, ice, laser treatment, manipulation under anaesthesia, suprascapular nerve block, non-steroidal anti-inflammatory drugs (oral, topical or intra-articular injection), opioid analgesics, paracetamol, physiotherapy (manual treatment, exercises), platelet-rich plasma injection, rotator cuff repair, shoulder arthroplasty, and ultrasound.