Platelets play an essential role in atherothrombosis and for this reason they are the primary target of antithrombotic therapy in ischemic stroke. We discussed here the evidence for efficacy and safety of current knowledge in antiplatelet therapy for stroke prevention after an acute ischemic stroke or transient ischemic attack. After an acute episode, long-term antithrombotic therapy is essential for the secondary prevention of stroke recurrence and complications. Antiplatelet therapy for acute ischemic stroke (non-cardioembolic) or ischemic stroke consists of three antiplatelet drugs, in accordance with Food and Drug Administration (FDA) from the USA and also with the Guidelines published by the American Heart Association (AHA) and nevertheless with the Guidelines of the American Stroke Association (ASA), in 2014, for preventing vascular events, such as stroke. These are aspirin, clopidogrel and dipyridamole. Moreover, recent randomized clinical trials and the last Guidelines for stroke of AHA∕ASA, in 2018, also mention ticagrelor. All of these antiplatelet therapies, besides inhibiting acute arterial thrombosis, also interfere with physiological hemostasis. In conclusion, we can say that current recommendations focused primarily on the therapy with aspirin for the secondary prevention of stroke in patients that presented vascular events, such as ischemic stroke of non-cardioembolic cause or transient ischemic attack and, as appropriate, aspirin plus dipyridamol or clopidogrel. The new therapy with ticagrelor in secondary stroke prevention seems to be promising, but more randomized clinical trials are needed to accurately assess the safety and efficacy of this new antiplatelet drug.