Oral anticoagulation in patients with cerebral amyloid angiopathy is a therapeutic challenge. The association of cerebral amyloid angiopathy with intracerebral hemorrhage, a high mortality of intracerebral hemorrhage especially under oral anticoagulation and the high risk of recurrent bleeding require a multidisciplinary approach and a thorough risk-benefit analysis. Vitamin K antagonists increase the risk of intracerebral bleeding and the accompanying mortality by 60% and should be avoided if possible or reserved for special clinical situations (e.g. mechanical aortic valve replacement). Treatment with novel oral anticoagulants and antiplatelet drugs also increases the risk of cerebral bleeding and therefore needs a thorough risk-benefit evaluation. An interventional left atrial appendage closure is a promising therapeutic option especially in patients with an absolute arrythmia with atrial fibrillation. Furthermore, other clinical implications in patients with cerebral amyloid angiopathy are the subject of this review of the literature, such as special characteristics after acute ischemic stroke and the necessary secondary prophylaxis, with previous intracerebral hemorrhage and in patients with cognitive deficits.