Stroke is the first cause of disability and the second cause of mortality in the world. Oral anticoagulants have been proved to be effective in the primary and secondary prophylaxis of stroke not only in cardiac conditions but also in other pathologies such as the antiphospholipid syndrome. Though the efficacy of oral anticoagulants in the prevention of stroke has been consolidated in several conditions such as mechanical prosthesis, atrial fibrillation, and the antiphospholipid syndrome, their role is less clear in patent foramen ovale, interatrial septal aneurysm, dilated cardiomyopathy, and aortic plaques. Nevertheless, oral anticoagulants have recently been re-evaluated in large clinical trials and have been shown to be effective in the secondary prevention of myocardial infarction and stroke. This review considers both the established and controversial aspects and the role of anticoagulation clinics in the practical approach to these patients, as well as their education and quality of life.