T-cells play an important role in the pathogenesis of many diseases. These include diseases with large commercial markets and also with significant unmet medical needs, such as rheumatoid arthritis and asthma in addition to those with smaller markets such as organ transplantation. Lck, one of eight members of the Src-family of tyrosine kinases, is activated following T cell stimulation and is required for T cell proliferation and IL-2 production. Inhibition of Lck has been a target to prevent lymphocyte activation and acute rejection. In this review we amass different functions and different moieties which act as an lck inhibitor for the treatment of different diseases. In addition we provide an analysis of the properties of these compounds that account for the specificity required for the inhibition of one of eleven highly similar kinases.