The hypothalamus has been long considered important in feeding and other motivated behaviors. The identification of neuropeptides expressed in the hypothalamus has initiated efforts to better elucidate the underlying molecular mechanisms involved. The neuropeptides orexin and melanin-concentrating hormone (MCH) are expressed in the lateral hypothalamus (LH) and have been implicated in regulation of feeding behavior. Neurons expressing these neuropeptides have extensive projections to regions of the brain important for behavioral responses to drugs of abuse, raising the possibility that the pathways may also be important in addiction. Regulation of LH intracellular signaling pathways in response to drugs of abuse supports a role for the LH neuropeptides in addiction.