Antibodies targeting the extracellular domains of ErbB receptors have been extensively studied for cancer drug development. This work has led to clinical approval of monoclonal antibodies against the well-known oncogenes EGFR and ErbB2. Here we discuss the biological activities of ErbB4, a less-studied member of the EGFR/ErbB growth factor receptor family and speculate on the potential clinical relevance of antibodies targeting ErbB4. In addition to their significance as therapeutics, the role of ErbB4 antibodies in prognostic and predictive applications is surveyed.