Stroke is a leading cause of death and disability. Recently, there have been advances in the treatment of acute ischemic stroke aimed at re-establishing blood flow to the affected area in an effort to save the ischemic penumbra surrounding the area of infarction. This is achieved by the use of thrombolytics intravenously or intra-arterially. The use of mechanical devices facilitates the function of pharmacological agents used in addition to minimizing the associated risks. In this review, we first discuss the therapeutic potentials and strategies employed in using different thrombolytics in management of acute ischemic stroke. Subsequently, we discuss the recent advances and therapeutic applications of mechanical devices in this field.