This article reviews the current state of efforts targeting the ErbB family of tyrosine kinase receptors in cancer therapy. In particular, preliminary results will be discussed of studies of the first generation of therapeutics to enter clinical evaluation in malignant diseases. Results of recently conducted clinical studies with ZD1839 (Iressa), OSI-774 (Tarceva), Cetuximab (IMC-C225) and trastuzumab (Herceptin) and several other compounds are presented. Potential advantages and disadvantages of these different therapeutic modalities, as well as future challenges of evaluating ErbB-targeted agents in the clinic, are presented.