Dasatinib is a potent oral tyrosine kinase inhibitor which targets several kinases, including the SRC family kinases. SRC family kinases have been implicated in androgen therapy resistance that often develops in metastatic castration-resistant prostate cancer (mCRPC), which drives the need for non-androgen targeting therapies. This article describes the preclinical rationale for the use of combination dasatinib and docetaxel therapy in mCRPC, and highlights the results of a phase I-II trial in which 46 patients with mCRPC, treated with a regimen of dasatinib and docetaxel, demonstrated improvements in bone scans, high rates of soft tissue responses, and modulation of markers of bone turnover. This brief report discusses in detail follow-up data on two patients who remain alive after >2.5 years on dasatinib single-agent therapy after discontinuing docetaxel treatment.