Electronic learning (E-learning) is a method of acquiring knowledge by using information technology. In this regard, faculty members of medical schools play an important role in the design, development and institutionalization of electronic content education and face many challenges. Hence, the present study was performed to explore the challenges to the development and institutionalization of e-learning content as perceived by faculty members of medical schools in southern Iran. The present study is a descriptive qualitative study. Purposeful sampling was performed. Based on this, 23 individual and in-depth semi-structured interviews were conducted with 23 faculty members of medical schools. Granheim and Lundman's approach was used for data analysis. Three themes and eleven subthemes were extracted based on the qualitative data analysis results. Three main themes included individual challenges, organizational management challenges, and course design challenges. Based on the results of the present study, we should keep in mind that electronic teaching methods and preparation of e-learning content by professors are different from traditional educational methods. Hence, the senior managers of educational system should make necessary arrangements and plans for methodological support, technological and technical support, and all kinds of organizational support and create continuous professional development opportunities for professors to minimize the negative effects caused by the rapid changes of electronics era and educational environments on professors, and consequently on the quality of educational contents and processes.