While innovations in the surgical management of retinal detachment (RD) with proliferative vitreoretinopathy (PVR) have significantly improved anatomic and visual outcomes over the years, recurrent RD due to PVR remains the major limitation to success. There are currently no medical therapies proven to be effective against PVR in humans. Increased understanding of the pathophysiology and risk factors for PVR have helped guide investigations for molecular targets. Drugs that counteract inflammation, proliferation, and growth factors are the leading candidates for treatment of PVR. This review discusses the ongoing search for pharmacologic therapies, with an emphasis on the results of recent clinical investigations.