OBJECTIVE: Large artery atherosclerosis is a common cause of ischemic stroke and transient ischemic attack and presents a high-risk condition for recurrent strokes. This article provides clinicians with current best practices in the diagnosis and management of large artery atherosclerosis. LATEST DEVELOPMENTS: With an aging population and high prevalence of poorly controlled risk factors, the incidence of stroke due to atherosclerosis will continue to increase. Aggressive management of risk factors, including hypertension and hyperlipidemia, is an essential part of managing patients with stroke or transient ischemic attack due to large artery atherosclerosis. Dual antithrombotic therapy for secondary stroke prevention is recommended for more patients with large artery atherosclerosis than ever before. The role of revascularization, particularly for asymptomatic carotid disease, continues to be explored in the era of better medical management practices. ESSENTIAL POINTS: Preventing ischemic stroke in patients with large artery atherosclerosis is largely reliant on providers aggressively managing stroke risk factors, ensuring appropriate antithrombotic selection, and carefully selecting patients for revascularization.