Research participants randomized to placebo-control conditions often report improved outcomes and can manifest physiologic responses that mirror those of participants who received the bioactive compound. Recent studies show that placebos can have beneficial effects even when the individual is aware that he/she is receiving a placebo, suggesting that the therapeutic context in which a placebo is delivered can be powerful. This context includes environmental and psychosocial factors, such as information disclosure, expectations, conditioning and empathy, embedded within research and clinical encounters that may influence outcomes. In this article, we review these placebo-related factors (PRFs), consider how they may influence the results typically attributed to diet and lifestyle interventions, and offer suggestions on enhancing PRFs in clinical obesity settings.