Cosolvent molecular dynamics (MD) simulations use small organic probe molecules to sample along a protein surface and identify binding "hotspots". The benefits of this approach are the protein can adapt to the presence of the cosolvents and the cosolvents must compete with water to interact with the protein. Accommodating protein flexibility and hydration effects are two leading challenges in structure-based drug discovery. Advances in cosolvent MD will be presented including applications to allosteric systems, prediction of bridging water molecules, identification of cryptic binding sites, and assessment of target druggability. Though these approaches are resource intensive, they have the promise of identifying previously unknown regulatory sites on proteins, which could significantly increase the number of drug targets available to treat a wide variety of medical disorders.