Functional dyspepsia (FD) is subdivided into epigastric pain syndrome and postprandial distress syndrome according to the Rome IV consensus. Based on the assumption that disordered gastric motility is a key pathophysiologic factor in postprandial distress syndrome, prokinetic agents are often proposed as the treatment of choice for this subgroup. Although a meta-analysis suggests that prokinetic agents may be efficacious and safe in FD, there is a lack of widely available agents of proven efficacy. This review analyzes some of the difficulties and challenges in establishing therapeutic efficacy of prokinetic drugs in FD.