Several directions are currently being explored to improve treatment outcome among patients with breast cancer. Although regulation of cell division likely will be necessary to effect an ultimate cure for cancer, work continues into maximizing responses to chemotherapy to manage the neoplastic progression and symptoms of disease. While new anticancer agents are being sought, progress has been most readily achieved through the concepts of drug dosing and scheduling. Manipulating treatment impact by altering drug intensity and using novel scheduling strategies are yielding improvement in responses, and newer concepts, such as the limits of cytoreduction, are gaining prominence in clinical trials. This article reviews the current knowledge, ongoing research protocols, and future directions in these areas of systemic therapy for breast cancer.