Episodic future thinking allows humans to mentally simulate virtually infinite future possibilities, yet this device is fundamentally goal-directed and should not be equated with fantasizing or wishful thinking. The purpose of this fMRI study was to investigate the neural basis of such goal-directed processing during future-event simulation. Participants were scanned while they imagined future events that were related to their personal goals (personal future events) and future events that were plausible but unrelated to their personal goals (nonpersonal future events). Results showed that imaging personal future events elicited stronger activation in ventral medial prefrontal cortex (MPFC) and posterior cingulate cortex (PCC) compared to imaging nonpersonal future events. Moreover, these brain activations overlapped with activations elicited by a second task that assessed semantic self-knowledge (i.e., making judgments on one's own personality traits), suggesting that ventral MPFC and PCC mediate self-referential processing across different functional domains. It is suggested that these brain regions may support a collection of processes that evaluate, code, and contextualize the relevance of mental representations with regard to personal goals. The implications of these findings for the understanding of the function instantiated by the default network of the brain are also discussed.