Leptomeningeal metastasis is a fatal manifestation seen in advanced cancer patients. Its incidence is increasing, reaching 3.8% in molecularly unselected non-small cell lung cancer patients and up to 5% and 9% in ALK-rearranged and EGFR-mutant lung cancer patients, respectively. The prognosis remains poor despite systemic treatment, intrathecal chemotherapy, radiation therapy and personalized treatments in molecularly selected patients. However, new therapies with improved cerebral-spinal fluid penetration have been developed for subgroups of molecular selected patients indicating they could be promising therapeutic options for managing leptomeningeal disease. Systemic chemotherapy, which may be combined with intrathecal chemotherapy, remains standard treatment for lung cancer patients with leptomeningeal disease and a good-risk profile. We summarize evidence reported in the literature for managing this complication in lung cancer patients. Based on this, we have selected potential therapeutic strategies that could be used in daily clinical practice.