Stroke is a multifactorial disease and several risk factors might contribute to its pathogenesis, both in isolation and in association. The close dependency to these risk factors in the whole population provides a relevant chance to prevention. In particular, patients with a past history of stroke are at high risk of stroke recurrence (about 9 times higher than the corresponding age and sex matched patients without a stroke, whilst the corresponding risk of recurrence for myocardial infarction is four times) and an aggressive strategy of secondary prevention is needed, targeting all risk factors (e.g., arterial hypertension, hyperlipidemia, diabetes, and atrial fibrillation) with drug and lifestyle interventions. A special situation is constituted by large artery atherosclerosis both in extracranial and intracranial arteries, whose therapeutic strategy is addressed in detail.