Dopamine (DA) is arguably one of the most important and most studied neurotransmitters, and it is plays an important role in a wide range of brain functions. In humans, functional magnetic resonance imaging (fMRI) signals within the human mesolimbic system, including the dopaminergic midbrain (substantia nigra/ventral tegmental area; SN/VTA) and the ventral striatum, have been associated with the processing of reward-related stimuli as well as with the cognitive processes and actions required to obtain the reward. Beyond these well-known reward-anticipation responses within the human SN/VTA complex, this region appears to be engaged in the processing of other kinds of salient information, including stimulus novelty, which in turn has important implications for hippocampal memory formation. In recent human fMRI studies, we observed interactions between the key areas of the reward and memory systems that are consistent with animal models of the involved DA-dependent mechanisms. Specifically, novelty enhanced typical reward-anticipation responses within the SN/VTA complex, suggesting an exploration bias for novel stimuli. At the same time, reward facilitated hippocampal memory formation, suggesting an encoding bias for reward-predictive stimuli. Moreover, these processes appear to be mediated by inter-individual differences, including personality traits as well as DA-related genetic polymorphisms and DA-receptor properties. Although fMRI cannot directly visualize neurotransmitter activity, converging evidence from primate and human studies employing pharmacological MRI and positron emission tomography (PET) suggests that fMRI responses to reward and novelty are linked to DA-neuron activity at the level of the midbrain and the post-synaptic effects of DA release in the target regions.