The role-play for pharmacological education has been developed by Yanagita et al. since 2010 and incorporated into the curriculum of more than 20 medical or pharmaceutical universities in Japan. This case and communication based active learning course provides the practice to acqire fundamental competences for drug therapy, through role playing of medical professionals and patients in simulated clinical settings. The online pharmacological role-play for the first time was performed at Tohoku Medical and Pharmaceutical University Faculty of Medicine during the state of emergency in Japan. We found that the online role-play was as useful as face-to-face role-plays to train appropriate drug prescriptions and communication skills in medical students. In this review, we described the course design, preparation, and operation of online role-play for pharmacological education. We also explained the differences, advantages, and disadvantages between online and face-to-face setting. Finally, we gave examples on-going challenges to the effective use of the online role-play as a core curricular model of pharmacological and pharmacotherapeutic education.