Aromatase Inhibitors (AI) are widely used for the adjuvant treatment of hormone receptor positive breast cancers in the post-menopausal population. AI are often associated with significant joint and muscular symptoms; symptoms that are commonly referred to as aromatase inhibitor-associated musculoskeletal syndrome (AIMSS). AIMSS adversely impacts health-related quality of life of many patients, and reduces AI compliance. Although there are informal practice recommendations, the limited current level of evidence for management of AIMSS for breast cancer patients on aromatase inhibitors has made development of formal guidelines challenging, and remains an unmet need. This is the first systematic review to consider the evidence for all pharmacological and non-pharmacological interventions in the treatment of AIMSS, including physical therapy, acupuncture and complementary therapies.