Due to the significant increase in interest in placebos, biomedical scientists have incorporated placebo innovations into a modern methodological research scenario in order to increase the quality of clinical studies. Indeed, the randomised-controlled trial design has changed dramatically, and these changes have had an impact on manual therapy research as well. The present paper outlines the main difficulties that placebo-controlled trials pose for research in manual therapy, for example, designing ineffective sham protocols, the role of touch in triggering neurobiological responses, or the unique specificity of manual therapies. The paper then offers suggestions on how to overcome such challenges, for example by providing a definition of ‘specificity’ in the context of manual therapies, and specifically osteopathy, suggesting how to design adequate sham procedures, and by introducing the so-called ‘touch equality assumption'