Breast cancer, the most commonly occurring cancer in women in the United States, is the second most common cause of cancer-related mortality. Mortality rates in breast cancer have, however, declined by 2.3% per year from 1990 to 2001, partly because of the development of better chemotherapy agents and regimens, which have resulted in major changes in the standards of care. To study the changes in the past decade in expert opinion about the preferred chemotherapy for breast cancer, we compared the treatment guidelines of the National Comprehensive Cancer Network (NCCN) for 1996, 2000, and 2005. The myelotoxicity associated with the NCCN-recommended agents was also assessed by using data from the prescribing information for the drugs. This review showed that many of the agents, combinations of agents, and new dosing schedules currently recommended in the NCCN guidelines for the treatment of breast cancer are associated with myelosuppression. Many of these myelosuppressive regimens, which were used in the past to treat advanced-stage or metastatic disease, are now prescribed for early-stage disease. Furthermore, the cytotoxic agents and regimens recommended by the NCCN are more myelosuppressive than those recommended a decade ago. Many oncologists are aware of this trend toward the more intensive treatment of patients with cancer and take proactive steps to minimize the risk of myelosuppression and its complications.