Lung, breast, and colorectal cancers are the 3 most frequent causes of cancer-related death in the United States. In the past 15 years, survival has increased dramatically for patients with these tumor types, partly because improved chemotherapy caused major changes in standard care. In addition, maintaining chemotherapy dose intensity has an established a positive effect on patient outcomes. However, delivering chemotherapy at full dose and on schedule is limited primarily by myelosuppression. To determine how expert opinion about preferred chemotherapy for lung, breast, and colorectal cancers has changed over the past decade, the National Comprehensive Cancer Network (NCCN) treatment guidelines from 1996, 2000 or 2001, and 2005 for each tumor type were compared. The myelosuppressive potentials of NCCN-recommended agents were assessed using data from their prescribing information. Many agents and combinations of agents recommended in the NCCN guidelines for treating lung, breast, and colorectal cancers are associated with myelosuppression. Several of these myelosuppressive regimens, which were previously recommended for treating advanced-stage or metastatic disease, are now preferred for early-stage disease, and neoadjuvant or adjuvant therapy is now recommended in more tumor types and stages than ever before. These findings indicate that the cytotoxic agents and regimens recommended today are associated with more myelosuppression than those preferred a decade ago and are more widely used in early-stage disease when survival benefits are possible. Because of this trend toward more intensive treatment of patients with cancer, proactive steps should be taken to minimize the risk for myelosuppression and its complications while optimizing the relative dose intensity.