Stroke continues to be a significant public health problem worldwide. Despite a number of clinical trials testing various therapeutic agents, we are still left with a small armamentarium of options. Aspirin, clopidogrel and combination aspirin-dipyridamole remain the mainstay for prevention of recurrent ischemic stroke. Tissue plasminogen activator (tPA) or alteplase is the sole agent used in the acute phase up to 4.5 h from the onset of stroke symptoms. A greater understanding of pathophysiologic mechanisms produced an array of acute experimental treatments including intravenous magnesium and free radical scavengers. However, they did not stand up to the scrutiny of phase III randomized clinical trials. Secondary prevention of stroke benefitted more from epidemiologic studies focusing on risk factor modifications, rather than antiplatelet or other stroke specific agents. One must ask if new treatments for stroke are exhausted. Despite the frustrations of stroke neurologists, new avenues for treatment continue to be explored. One comes from our colleagues in cardiology. Development of new medications for treating ischemic heart disease, acute or chronic, may provide opportunity to cross over into stroke. Cardiovascular trials usually encompass stroke as an outcome measure. As of yet, there have not been the data to support use of these agents in stroke. Recent medications for acute and chronic phases of ischemic heart diseases include desmoteplase, tenecteplase, tirofiban, prasugrel, and ticagrelor. Though some of these medications may fail to show a benefit in stroke patients, we feel there is always potential for a breakthrough.