Prospective memory (PM) refers to the ability to remember to do something in the future, either in response to an event (event-based) or after a certain amount of time has elapsed (time-based). While the distinction between event- and time-based PM is widely acknowledged in the literature, little is known about the processes they share and those they do not. This is particularly true concerning their brain substrates, as almost all neuroimaging studies so far have focused on event-based PM. We proposed a functional magnetic resonance imaging paradigm assessing both event-based and time-based PM to 20 healthy young individuals. Analyses revealed that event- and time-based PM both induced activation in the posterior frontal and parietal cortices, and deactivation in the medial rostral prefrontal cortex. In addition, activation more specific to each condition, which may underlie differences in strategic monitoring, was highlighted. Thus, occipital areas were more activated during event-based PM, probably reflecting target-checking, while a network comprising the dorsolateral prefrontal cortex, the cuneus/precuneus and, to a lesser extent, the inferior parietal lobule, superior temporal gyrus, and the cerebellum, was more activated in time-based PM, which may reflect the involvement of time-estimation processes. These results confirm the allocation of attentional resources to the maintenance of intention for event-based and time-based PM, as well as the engagement of distinct mechanisms reflecting the monitoring strategies specific to each condition. Hum Brain Mapp 35:3066–3082, 2014. © 2013 Wiley Periodicals, Inc.