Review of results of clinical studies indicates the number of potential patients who are actually treated for acute ischemic stroke is disappointingly low, and effective treatments are making a minor impact on this major public health problem. Imaging modalities, such as diffusion- and perfusion-weighted images, as well as CT perfusion and CT angiography, to better select patients for treatment are now routinely performed in most academic medical centers. However, there is not a perfect penumbra imaging technique and each one has its own advantages and disadvantages. Recent advances in molecular imaging modalities allow a better understanding of this pathophysiological process that could lead to enhanced therapy for stroke. This article seeks to describe the role of molecular imaging in identifying the pathophysiology of stroke and how it could be incorporated in future decision-making and treatment strategies in stroke.