The combination of breast-conserving surgery and radiation therapy is now accepted as a standard treatment option for most women with clinical stage I or II invasive breast cancer. The great majority of individuals with early stage breast cancer are potential candidates for treatment with conservative surgery and radiation therapy. Nonetheless, for a few patients, such treatment may be absolutely or relatively contraindicated due to toxicity concerns, poor anticipated cosmetic results, or a heightened risk of local failure. This article will discuss the patient, clinical, and pathologic factors relevant to selecting patients for this treatment approach.