With more data on the use of oxaliplatin and irinotecan available, and the recent approval of two signal transduction inhibitors for patients with advanced colorectal cancer, there are now many treatment options to choose from. From the current regimens no straightforward choice can be made that provides any patient with the optimal chance for prolonged survival with the least side-effects. The current data concerning timing and duration of chemotherapy, combination or sequential therapy, preference of agents for first-line treatment, oral fluoropyrimidines, neo-adjuvant chemotherapy for irresectable liver metastases, and the use of signal transduction inhibitors are reviewed.