Growing evidence reveals that mindfulness meditation significantly reduces pain responses in experimental and clinical settings. Recent neurobiological findings confirm that the cognitive state of mindfulness significantly modifies sensory, cognitive, and affective dimensions of nociceptive processing. However, there are likely nonspecific effects associated with mindfulness meditation-related pain relief that are also consistent with placebo-related responses. For instance, reports of pain relief during meditation may be associated with subjects’ expectation of analgesia related to the health promoting reputation of meditation, facilitator attention, report biases, and conditioning/extinction processes. With respect to the recent interest in meditation and the clinical utility of mindfulness-based mental training, it is important to determine if the pain-relieving effects of mindfulness meditation employ distinct brain mechanisms from those engaged by the placebo response. This presentation will disentangle and identify the neural mechanisms of action associated with mindfulness meditation-related pain relief as compared to placebo-analgesia and sham mindfulness meditation.