The mesolimbic dopaminergic system (ML-DA) allows adapted interactions with the environment and is therefore of critical significance for the individual's survival. The ML-DA system is implicated in reward and emotional functions, and it is perturbed in schizophrenia, addiction, and depression. The ML-DA reward system is not only recruited during wakeful behaviors, it is also active during sleep. Here, we introduce the Reward Activation Model (RAM) for sleep and dreaming, according to which activation of the ML-DA reward system during sleep contributes to memory processes, to the regulation of rapid-eye movement (REM) sleep, and to the generation and motivational content of dreams. In particular, the engagement of ML-DA and associated limbic structures prioritizes information with high emotional or motivational relevance for (re)processing during sleep and dreaming. The RAM provides testable predictions and has clinical implications for our understanding of the pathogenesis of major depression and addiction.