Cytotoxic chemotherapy continues to play a critical role in the optimal management of early-stage breast cancer, providing significant benefits in the risk of recurrence and survival. Anthracycline-based regimens are considered standard in the United States, and more recently, the addition of taxanes has proven efficacious, particularly for high-risk patients. One ongoing question in the adjuvant field has been the determination of appropriate therapy for patients with node-negative disease. Evolving treatment guidelines, computerized algorithms, and genomic tools might aid in evaluating individualized recurrence risks for this patient population. In addition, new cytotoxic agents and different drug combinations and treatment schedules are currently being investigated to optimize treatments for early-stage disease.