Brain metastasis occurs in approximately 30% of patients with ALK-positive non-small-cell lung cancer (NSCLC) at the time of diagnosis. In patients treated with crizotinib, CNS progression occurs in up to 70% of patients. Intracranial progression is believed to be a result of acquired resistance to 1st line ALK inhibitor and inadequate penetration of drugs into the CNS. There are several options available for patients with brain metastasis, including surgical resection, whole-brain radiotherapy, stereotactic radiosurgery, or both of them. Due to recent introduction of effective targeted therapy with ALK-inhibitors, patients with advanced ALK positive NSCLC achieve high overall response rates and remain progression-free for long time intervals. Thus, patients with brain metastasis from ALK-positive NSCLC have a distinct natural history, compared with patients with ALK wild-type NSCLC. In the light of this, it needs to be discussed how treatment algorithms for managing patients with brain metastasis should be modified. Therefore, based on an updated review of the literature, this lecture provides an overview on the epidemiology and the treatment of patients’ brain metastasis. It describes the specifics of ALK-positive disease and proposes an algorithm for the treatment of patients with advanced ALK-positive NSCLC and brain metastasis.