Cancer is the second largest cause of death after cardiovascular disease in the United States. Systemic chemotherapy is the major treatment modality for a number of common cancers, such as lymphomas, leukemias, and for the majority of disseminated tumors. The emergence of drug-resistant tumor cells is the major cause of subsequent cancer treatment failures. Overcoming drug resistance is a difficult problem that remains unresolved; results to date suggest that tumor drug-resistance will continue to be a major limitation to success with anticancer chemotherapy. Short term, a multi-disciplinary treatment of cancer (eg, via cancer centers) should seek to eradicate cancer effectively at the time of diagnosis, with encouragement of patients to participate in clinical trials (eg, adjuvant chemotherapy). Long-term goals for cancer management should include cancer prevention and early detection through intensive public education, incentives for participation in early detection programs, and continued research, with a focus on mechanisms of tumor drug-resistance.