The epidermal growth factor receptor (EGFR) is expressed in a wide variety of solid tumours. It has been demonstrated that the EGFR-associated signaling pathway plays an important role in carcinogenesis and cancer progression. In the new therapeutic paradigm of molecular-targeted cancer therapy, interference with intracellular signaling cascades is an appealing treatment approach. Inhibitory strategies under study include monoclonal antibodies, tyrosine kinase inhibitors, EGFR-ligand conjugates, EGFR immunoconjugates, and antisense oligonucleotides. Many of these strategies have demonstrated efficacy against EGFR-expressing tumour cells in preclinical studies, prompting a large number of clinical trials. In particular, clinical studies using monoclonal antibody blockade and EGFR tyrosine kinase inhibitors have suggested that EGFR blockade is a well-tolerated and effective treatment strategy; however, more trials are needed to precisely define how these agents will fit into modern cancer care.