The epidermal growth factor receptor (EGFR), a growth factor receptor involved in the regulation of cellular differentiation and proliferation, is highly expressed by many tumor cells. In light of a relationship between overexpression of EGFR and clinically aggressive malignant disease, EGFR has emerged as a promising target for cancer therapy. In recent years, several molecular strategies have been explored to modulate either the EGFR itself, or the downstream signal beyond the cell surface receptor. One of the most promising current strategies involves the use of anti-EGFR monoclonal antibodies (mAbs), either alone or in combination with conventional cytotoxic modalities such as chemotherapy or radiotherapy. This review focuses primarily on recent progress in the development of anti-EGFR mAbs, and examines their potential in the treatment of cancer.