Empirical findings have identified spirituality as a potential health resource. Whereas older research has associated such effects with the social component of religion, newer conceptualizations propose that spiritual experiences and the intrapersonal effects that are facilitated by regular spiritual practice might be pivotal to understanding potential salutogenesis. Ongoing studies suggest that spiritual experiences and practices involve a variety of neural systems that may facilitate neural 'top-down' effects that are comparable if not identical to those engaged in placebo responses. As meaningfulness seems to be both a hallmark of spirituality and placebo reactions, it may be regarded as an overarching psychological concept that is important to engaging and facilitating psychophysiological mechanisms that are involved in health-related effects. Empirical evidence suggests that spirituality may under certain conditions be a predictor of placebo response and effects. Assessment of patients' spirituality and making use of various resources to accommodate patients' spiritual needs reflect our most current understanding of the physiological, psychological and socio-cultural aspects of spirituality, and may also increase the likelihood of eliciting self-healing processes. We advocate the position that a research agenda addressing responses and effects of both placebo and spirituality could therefore be (i) synergistic, (ii) valuable to each phenomenon on its own, and (iii) contributory to an extended placebo paradigm that is centred around the concept of meaningfulness.