In recent years, screen-based technologies have changed the way we communicate, study and consume goods, entertainment and information. Thus, our environment has changed profoundly, and it is reasonable to assume that children today have a different developmental environment compared to the past, making it crucial to understand the impact of our technology-rich environment on development as well as on physical and psychological well-being. The goal of the present paper is to provide a comprehensive review of randomized controlled studies assessing effects of screen use on physiology and behavior, in order to give as wide as possible a picture of screen use and its various effects. We conclude with a discussion focusing on the ability to reach “bottom lines” regarding the down- and upsides of screen-use. We also highlight and discuss the major areas in which knowledge about the effects of screens is lacking, requiring further high-quality and well-controlled studies.