c-Src was the first protooncogene described and was among the first molecules in which tyrosine kinase activity was documented. c-Src has been defined as a common modular structure that participates in much of the crosstalk between the cytoplasmic protein tyrosine kinases and tyrosine kinase receptors. Understanding the structure and function of this important class of protein kinases and elucidating the molecular signaling events mediated by c-Src are important not only for identifying the critical pathways but also for designing new strategies to block or inhibit the action of these kinases. Despite the large amount of information available on c-Src, its precise functions in cancer remain to be elucidated. Recently, there has been renewed interest in c-Src as a molecular target for cancer therapy, and multiple c-Src inhibitors are entering clinical trials. In this review, the authors describe the function and expression of c-Src in human malignancies and the novel c-Src inhibitors and their potential applications for cancer treatment. Cancer 2006. © 2006 American Cancer Society.