The ERBB family of receptor tyrosine kinases has a central role in the tumorigenesis of many types of solid tumour. Various therapeutics targeting these receptors have been approved for the treatment of several cancers. Considerable preclinical data have shown that the administration of two inhibitors against an individual ERBB family member--particularly epidermal growth factor receptor (EGFR) or ERBB2--leads to markedly higher antitumour activity than the administration of single agents. This Opinion article describes the preclinical and clinical performance of these dual-targeting approaches, discusses the key mechanisms that mediate their increased efficacy and highlights areas for ongoing investigation.