Preclinical evaluation of purported acute stroke therapies plays a significant role in the drug development process. Animal stroke models and their use in evaluating treatment effects of potential acute stroke therapies are prone to many difficulties. Recently, it has been proposed that diffusion-perfusion MRI might help to bridge the gap between preclinical evaluation and advanced clinical trials. Several reports have appeared concerning the use of PWI and DWI to assess thrombolytic therapy in animal stroke models. Combining Perfusion MRI (PWI) and Diffusion MRI (DWI) in temporary occlusion models evaluating neuroprotective drugs may also be useful. The use of diffusion-perfusion MRI both in preclinical testing and in clinical development of acute stroke therapies will likely continue to expand, especially once the MRI modalities provide support for the approval of a new acute stroke therapy. Their utility will also increase as we move into the multitherapy era of acute stroke therapy.