INTRODUCTION: Breast pain may be cyclical (worse before a period) or noncyclical, originating from the breast or the chest wall, and occurs at some time in 70% of women. Cyclical breast pain resolves spontaneously in 20% to 30% of women, but tends to recur in 60% of women. Non-cyclical pain responds poorly to treatment but tends to resolve spontaneously in half of women. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for breast pain? We searched: Medline, Embase, The Cochrane Library, and other important databases up to May 2010 (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). RESULTS: We found 24 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: antibiotics, bromocriptine, combined oral contraceptive pill, danazol, diuretics, evening primrose oil, gestrinone, gonadorelin analogues, hormone replacement therapy (HRT), lisuride, low-fat diet, progestogens, pyridoxine, tamoxifen, tibolone, topical or oral non-steroidal anti-inflammatory drugs (NSAIDs), toremifene, and vitamin E.