Src is the cellular counterpart of the first identified viral oncogene v-Src. It forms part of a large family of nonreceptor tyrosine kinases that have been extensively studied over the last few decades. This has led to the realization that Src can regulate a number of signaling pathways that impact on the behavior of tumor cells, including proliferation, survival, migration, invasion, and angiogenesis. There are currently four Src inhibitors (dasatinib, saracatinib, bosutinib, and KX01) in clinical development, and although there is a plethora of information on their activity in preclinical models their clinical efficacy has been disappointing. Here we review the current status of the Src inhibitors and highlight the difficulties involved in assessing these therapeutics in the clinical setting. In the future it will be important to combine our knowledge of basic Src biology with the use of appropriate preclinical models to aid the design of clinical trials. Taking this integrated approach will hopefully help to realize the true potential of Src kinase inhibitors.