Among the many chemotherapeutic options for metastatic colorectal cancer, none has shown clear superiority in efficacy. All pharmacologic agents in current use have been associated with adverse events. Frequently reported adverse events associated with the chemotherapeutic agents oxaliplatin, irinotecan, 5-fluorouracil, and capecitabine include acute and chronic neuropathy, hypersensitivity reactions, diarrhea, neutropenia, and hand-foot syndrome. Although biologic agents are seemingly less toxic, toxic effects can also arise with their use; antiangiogenic agents result in hypertension, and EGFR inhibitors can cause severe hypersensitivity, paronychial infections, and more commonly, dermatologic rash. Furthermore, a correlation has been reported for the efficacy of anti-EGFR agents and development of rash. Data indicate that elderly patients with colorectal cancer who have adequate function and performance status, who may previously have been dissuaded from pursuing active therapy solely on the basis of age, should receive the same treatment as younger patients. To enhance the survival of patients with metastatic colorectal cancer, many therapies are administered. Recognition of treatment-emergent toxic effects will, therefore, aid the design and implementation of management strategies that minimize treatment interruption and/or discontinuation, and enhance quality of life for patients.