The ErbB receptors are localized to the cell membrane where they are activated by ligand to trigger a network of signaling pathways. In some cancer cells, dysregulation of ErbB-mediated signaling confers a growth advantage, resulting in cellular transformation and increased metastatic potential. Several agents that inhibit individual ErbB receptors have recently been approved for the treatment of human malignancies, validating ErbB receptors as therapeutic targets. One strategy to improve the efficacy of ErbB-targeted therapies is to inhibit multiple ErbB receptors, thereby interfering with the cooperation that exists between receptors. This minireview addresses the approaches being developed to concurrently inhibit multiple ErbB receptors.