ADAM15 is a widely expressed multi-domain protease that has been implicated in the pathogenesis of many human diseases. Given the diversity of the ADAM15 functional domains, this protease is thought to affect several important cellular processes, including cell adhesion, degradation of extracellular matrix components, and ectodomain shedding of membrane-bound growth factors that are intrinsic to cancer and various inflammatory conditions. The multiple levels by which the activity of ADAM15 can be regulated include signal transduction, modulation of catalytic function, spatial regulation, and post-translational modifications. Taken together, this multi-functional disintegrin protease not only offers a variety of potential targets for therapeutic intervention, but also represents an attractive target for pharmaceutical consideration due to its involvement in key cellular processes and various disease states. Modalities aimed at inhibiting protease activation, metalloproteinase activity, or integrin binding capability could prove beneficial for the treatment of cancer and inflammatory diseases.