OBJECTIVES: The objective of this systematic review was to identify treatment guidelines for metastatic colorectal cancer (mCRC) and to assess guideline recommendations. METHODS: Publications were identified through electronic searches of MEDLINE, MEDLINE In Process, EMBASE and the Cochrane Library; through manual searches of the reference lists of relevant articles; and by searching websites on the Internet. The MEDLINE and EMBASE searches were limited to articles published in English, whereas the Cochrane library search had no language restrictions. RESULTS: A total of 1,633 citations/abstracts were identified from electronic database searches. Of these, 91 underwent full-paper review and 32 were included in the final analysis. In addition, 25 articles were identified from manual and website searches, giving a total of 57 guidelines. The guidelines were published between 1996 and 2010, with the majority published between 2004 and 2010. The country publishing the most guidelines was the USA (12), followed by the UK (10), Canada (8), France (8), Germany (3), Australia (2), Spain (2) and Italy (1). In addition, eight European and three International guidelines were identified. As monoclonal antibody therapy for mCRC was not introduced until 2004, no firm recommendations for monoclonal antibody therapy were made in guidelines published between 2004 and 2006. Recommendations for monoclonal antibody therapy first appeared in 2007 and evolved as more data became available. The most recent international, European, and US guidelines recommended combination chemotherapy with a monoclonal antibody for the first-line treatment of mCRC, while second-line treatment varied depending on the first-line regimen used. Cetuximab and panitumumab were recommended in patients with wild-type KRAS mCRC. CONCLUSIONS: The findings from this systematic review indicate that these recent treatment guidelines have recognized the role of monoclonal antibodies in the management of mCRC; and timely treatment guideline updates are necessary to reflect the most recently available data.