Numerous advances in the treatment of patients who have metastatic disease have improved colorectal cancer management, including new chemotherapeutic agents and combinations and targeted agents that modulate the efficacy of chemotherapy. Recent advances in the administration of irinotecan and oxaliplatin, in combination with 5-FU/LV, plus the addition of targeted agents bevacizumab and cetuximab have afforded steady increases in response rates and survival. Ongoing studies are evaluating the optimal sequencing and combinations of the agents described and the efficacy of new combinations in metastatic and adjuvant settings. Because the number of African-American patients in most clinical trials in colorectal cancer has been low, it is imperative that method increase participation so that new research developments reach all segments of the population.