The selection of therapy for women with metastatic breast cancer requires consideration of many factors. Multiple treatment options are available, including hormonal therapy, chemotherapy, and biologic therapy. Many issues exist regarding choice of agent(s), combination therapies, sequencing, and duration of therapy. Oncology nurses must understand the rationale behind the approaches so they can effectively administer the agents and monitor for side effects. Such knowledge enhances treatment-option counseling for patients, thus promoting a sense of well-being for patients with breast cancer. This article reviews strategies for the initial treatment of metastatic breast cancer and for later lines of treatment when resistance develops. It also provides nursing perspective on clinical factors that arise during the course of treatment.