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The importance of music in our daily life has given rise to an increased number of studies addressing the brain regions involved in its appreciation. Some of these studies controlled only for the familiarity of the stimuli, while others relied on pleasantness ratings, and others still on musical preferences. With a listening test and a functional magnetic resonance imaging (fMRI) experiment, we wished to clarify the role of familiarity in the brain correlates of music appreciation by controlling, in the same study, for both familiarity and musical preferences. First, we conducted a listening test, in which participants rated the familiarity and liking of song excerpts from the pop/rock repertoire, allowing us to select a personalized set of stimuli per subject. Then, we used a passive listening paradigm in fMRI to study music appreciation in a naturalistic condition with increased ecological value. Brain activation data revealed that broad emotion-related limbic and paralimbic regions as well as the reward circuitry were significantly more active for familiar relative to unfamiliar music. Smaller regions in the cingulate cortex and frontal lobe, including the motor cortex and Broca's area, were found to be more active in response to liked music when compared to disliked one. Hence, familiarity seems to be a crucial factor in making the listeners emotionally engaged with music, as revealed by fMRI data.