Following the milestone discoveries that identified Src as the first known protein tyrosine kinase and as a prototype oncogene, as well as Src transgenic studies to validate it as a promising therapeutic target for osteoporosis, intense efforts are being made to create Src inhibitor drugs. Drug discovery strategies focused on both the non-catalytic and catalytic domains of Src have successfully resulted in promising Src inhibitor lead compounds with potential therapeutic applications for osteoporosis, cancer, and other diseases. Some noteworthy examples of Src inhibitors are described, and their chemical diversity, structure-based design, and biological activities in vitro and in vivo are illustrated. The potency, selectivity, and in vivo efficacy of key Src inhibitors are being investigated in molecular, cellular and animal models. Consequently, Src inhibitor drug development is imminent, and current studies are well-poised to achieve the ultimate milestone of a Src inhibitor therapeutic.