Anti-EGFR molecules with monoclonal antibodies or tyrosine protein kinase inhibitors represent a strategy which remains promising as targeted therapies of cancers, despite some ambiguous results. This review proposes to expose the state of the art concerning the development of anti-EGFR molecules: rationale of this approach, analysis of the results obtained on the one hand by monoclonal antibodies and on the other hand by tyrosine kinase inhibitors. Finally, a presentation is done about possible predictive factors for a relevant use of these molecules in the future.