Summary: The alarming global increase of obesity and related complications suggests an urgent need for new therapeutic strategies. Strong evidence shows that obesity and diabetes are regulated by hypothalamic neurons, creating a new paradigm in the management of these diseases by targeting neurons. Up to now, neuron-related diseases are not adequately treated due to the lack of approaches to effectively reach specific cell populations. A major obstacle to improve clinical outcomes of central therapies relies on the inability to deliver therapeutically relevant doses of the drug/cargo to diseased cells or regions. Other factors such as blood brain barrier crossing, off target effects, toxicity and chemical instability also limit the treatment of these pathologies. Nanomedicine-based approaches provide promising opportunities for overcoming these limitations.