Targeted therapy refers to anticancer treatment which specifically targets key molecules of cancer cells and/or neovascular cells, aiming to thus interfere with processes of tumorigenesis, cancer progression and metastasis. The epidermal growth factor receptor (EGFR) was the first receptor to be proposed for targeted cancer therapy, having been found to be commonly overexpressed in a range of solid tumors and play a role in cancer cell proliferation, apoptosis, angiogenesis, invasion and metastasis. Despite successful development of EGFR-targeted pharmacological agents, clinical and molecular studies have indicated several limitations to the broad application of this treatment as a monotherapy. Novel combination treatments which might optimize the effect of EGFR inhibition have, therefore, been investigated. Research conducted into the mechanisms of action and synergy of these combination treatments is likely to enhance the role of the EGFR target in future cancer treatment.