OBJECTIVES: Metastatic bone lesions lead to an increase in the risk for skeletal related events (SREs), including pathologic fracture, spinal cord compression, hypercalcemia of malignancy, and severe bone pain requiring palliative radiotherapy or surgery to bone. Twenty-nine percent of breast cancer patients with bone metastases develop SREs. Our objective was to systematically review the literature on the impact of SREs on pain, quality of life (QOL), morbidity, survival and cost in breast cancer patients.   METHODS: We searched PubMed, limiting to peer-reviewed English-language human studies published in 2000-2010. The search was based on a SRE definition accepted by the U.S. Food and Drug Administration and European Medicines Agency. Articles were included if they were randomized-controlled trials, clinical trials with appropriate control group, systematic reviews, meta-analyses, case-series or economic analyses, and were excluded if they did not provide interpretable results on outcomes of interest. RESULTS: A total of 209 articles were screened, of which 131 were excluded, and 78 were abstracted.  No studies, outside of bisphosphonate trials, were identified that examined the impact of SREs as a group on clinical outcomes.   Bisphosphonate treatment reduced SREs, and hence improved pain and QOL. Literature indicated that presence of pathologic bone fractures is correlated with increased risk of death.  Spinal cord compression significantly impaired ambulatory function and shortened survival of these patients compared to historical controls.  Radiation therapy improved pain and QOL while bone surgery was shown to improve pain and function with vertebrectomy.  Limited evidence suggested treatment cost of SREs is $14,000 (95% CI: $11,000-$17,000) per patient. CONCLUSIONS:   Presence of clinical SREs is associated with worse morbidity and survival, while their treatment is associated with improved pain, QOL and morbidity among breast cancer patients.  SREs appear to increase cost of treatment substantially.