Triple-negative breast cancers represent a subset of breast cancers with a particularly aggressive phenotype and poor clinical outcomes. Recent molecular profiling of these tumors has revealed a high frequency of epidermal growth factor receptor (EGFR) dysregulation, among other abnormalities. EGFR status correlates negatively with survival in patients with triple-negative breast cancers, and thus focus has turned on this receptor as a potential clinical target. Two classes of EGFR inhibitors are currently in clinical use: the monoclonal antibodies and the small molecule tyrosine kinase inhibitors. Trials of these drugs in breast cancer, however, have been largely disappointing. It remains to be seen whether advances in our understanding of the mechanisms of EGFR dysregulation and effects of multiple compensatory pathways in breast cancer, coupled with improved targeting to appropriate patient populations, will yield meaningful improvements in clinical outcomes.