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Leptomeningeal disease (LMD) or leptomeningeal metastases (LM) occurs when tumor cells invade the leptomeningeal and cerebrospinal fluid (CSF) space. Melanoma is the most common cancer causing LMD (M-LMD). Its biology and pathophysiology are very poorly understood. Research efforts are being made to explore the mechanisms underlying the immune landscape and antitumor response in LMD. The significant advances in immunocellular and targeted therapies in unresectable or metastatic melanoma in the last decade have not translated to patients with LMD and the prognosis for these patients remains dismal. While several reviews in LMD have provided an overview including challenges in diagnosis and treatment, herein we highlight evidence-based findings with a focus on immunocellular and radiation therapies, as well as the challenges that we need to overcome to help breach the existing gap in research and treatments in M-LMD. This could potentially guide additional research avenues and a better understanding of the needs and challenges of M-LMD to find novel therapies and improve patient survival.