The treatment of colorectal cancer has advanced over the past several years with the introduction of several active agents. Determining which patients to treat with chemotherapy and choosing optimal treatment would allow practioners to maximize the benefit of chemotherapy. Several prognostic and predictive markers have been identified and include oncogenes, tumor suppressor genes, genes involved in angiogenic and apoptotic pathways and cell proliferation, and those encoding targets of chemotherapy. Specifically, prognostic markers include deletion of 18q (DCC), p27 and microsatellite instability. Predictive markers are those that may determine efficacy of drugs used in colorectal cancer such as fluropyrimidines and oxaliplatin. Alterations in gene expression, protein expression and polymorphic variants in genes encoding thymidylate synthase, dihydropyrimidine dehydrogenase, and thymidine phosphorylase and excision repair cross-complementing genes (ERCC1) may be useful as markers for clinical drug response, survival and host toxicity. The integration of these prognostic and predictive markers would allow individualized treatment for patients, maximizing therapeutic effect and minimizing exposure to toxicity.