During the last decades a variety of telemedicine applications have been trialed worldwide. However, telemedicine is still an example of major potential benefits that have not been fully attained. Health care regulators are still debating why institutionalizing telemedicine applications on a large scale has been so difficult and why health care professionals are often averse or indifferent to telemedicine applications, thus preventing them from becoming part of everyday clinical routines. We believe that the lack of consolidated procedures for supporting decision making by health care regulators is a major weakness. We aim to further the current debate on how to legitimize decision making about the institutionalization of telemedicine applications on a large scale. We discuss (1) three main requirements--rationality, fairness, and efficiency--that should underpin decision making so that the relevant stakeholders perceive them as being legitimate, and (2) the domains and criteria for comparing and assessing telemedicine applications--benefits and sustainability. According to these requirements and criteria, we illustrate a possible reference process for legitimate decision making about which telemedicine applications to implement on a large scale. This process adopts the health care regulators' perspective and is made up of 2 subsequent stages, in which a preliminary proposal and then a full proposal are reviewed.