It is widely presumed that odor quality is a direct outcome of odorant molecular structure, but increasing evidence suggests that learning, experience, and context play important roles in human olfactory perception. Such data suggest that a given set of olfactory receptors activated by an odorant does not map directly onto a given odor percept. Rather, odor perception may rely on more synthetic, or integrative, mechanisms subserved by higher-order brain regions. Results presented here explore the specific role of human orbitofrontal cortex (OFC) in the formation and modulation of odor quality coding. Combining olfactory psychophysical techniques and functional imaging approaches, we have found that sensory-specific information about an odorant is not static or fixed within human olfactory OFC, but is highly malleable and can be rapidly updated by perceptual experience. Critically, the magnitude of OFC activation predicts subsequent behavioral improvement in olfactory perception. Our findings highlight the pivotal role of OFC in linking olfactory sensation, perception, and experience. It is worth considering that many of the current proposed functions attributed to the (distinctively mammalian) OFC are an extension of mechanisms that originally evolved to mediate response flexibility between chemosensory signals and appropriate behavioral actions.