Source memory research suggests that attempting to remember specific contextual aspects surrounding prior stimulus encounters results in greater left prefrontal cortex (PFC) activity than simple item-based old/new recognition judgments. Here, we tested a complementary hypothesis that predicts increases in the right PFC with tasks requiring close monitoring of item familiarity. More specifically, we compared a judgment of frequency (JOF) task to an item memory task, in which the former required estimating the number of previous picture encounters and the latter required discriminating old from new exemplars of previously seen items. In comparison to standard old/new recognition, both source memory and the JOF task examined here require more precise mnemonic judgments. However, in contrast to source memory, cognitive models suggest the JOF task relies heavily upon item familiarity, not specific contextual recollections. Event-related fMRI demonstrated greater recruitment of right, not left, dorso-lateral and frontopolar PFC regions during the JOF compared to item memory task. These data suggest a role for right PFC in the close monitoring of the familiarity of objects, which becomes critical when contextual recollection is ineffective in satisfying a memory demand.