Although patients with metastatic colorectal cancer have historically had a uniformly dismal prognosis, recent advances in chemotherapeutics and surgical techniques allow many patients to be treated with the potential for long-term survival and cure. Patients with potentially curable disease are those in whom multidisciplinary strategies including surgery can result in safe resection of all metastatic disease with negative margins. Although favorable outcomes using such strategies can increasingly be predicted, the presence of poor prognostic factors does not necessarily represent a contraindication to the use of a potentially curative strategy as long as a margin-negative resection can ultimately be obtained. Further analysis of the innovative strategies and techniques described in this article are needed to maximize cure rates in patients with this disease.