Anti-EGFR antibodies were designed to inhibit the receptor tyrosine kinase activity of EGFR by directly binding to the extracellular domain. Anti-EGFR antibodies have been approved or will be approved for use in Japan, the USA or Europe. Recently, many studies have investigated molecular markers can predict the response to anti-EGFR antibodies so as to discriminate responders and non-responders. Activating KRAS mutation has been shown to be a potent predictive marker of resistance to anti-EGFR antibodies. Moreover, BRAF mutations, PIK3CA mutations or loss of PTEN have also been shown to be other molecular markers to predict resistance to anti-EGFR antibodies. Further studies must integrate these markers into clinical decisions to use or not use anti-EGFR antibodies.