The hormone leptin, produced by fat cells, has been suggested as a potential obesity therapy. However, recent studies suggest that therapeutic approaches that deliver the leptin protein systemically may be problematic, indicating the need for targeting of the gene product to specific cells in the central nervous system. With this end in mind, Mulligan and colleagues have delivered leptin to the mouse hypothalamus by intracranial gene transfer using an adeno-associated viral vector, demonstrating efficient body weight control in obese mice (see p. 169).