This review is intended to summarize the literature on the modulation of the human reward system by estradiol. It will integrate previous neuroimaging findings in current rodent models, which suggest a dopamine-agonistic effect of physiological estradiol that may increase reward sensitivity in females. In human research, most neuroimaging studies have addressed menstrual cycle-related differences in reward-related brain activation and behaviors by comparing phases of high versus low estradiol availability. Few studies have also used pharmacological intervention to induce different hormonal states for comparisons of high and low estradiol, while others have also assessed the correlations between brain activation and state-related estradiol to infer causality. Since most human samples were small (n < 30) and the majority of studies used region-of-interest approaches or reported neuroimaging results that were incorrected for multiple comparisons, it is currently undetermined whether estradiol promotes human reward sensitivity to a similar extent as it does in rodents.