New research on orexin neurons may help explain how drug reward becomes an intense and unrelenting wanting, with wakefulness, concerted effort, and persistent pursuit. A small population of hypothalamic orexin neurons projects widely through the brain, influencing dopamine, stress, attention, and autonomic systems. Liking is pleasure when a reward is consumed; wanting is the sometimes-intense incentive pull making us seek a reward. However, temporarily suppressing orexin neurons during reward anticipation reduced responding and lowered the point at which the animals stopped trying. Activating orexin neurons shifted rats toward larger but less certain rewards—much as a large gambling win can disproportionately shape later choices.