Social networking sites (SNS), with Facebook as a prominent example, have become an integral part of our daily lives and more than four billion people worldwide use SNS. However, the (over-)use of SNS also poses both psychological and physiological risks. In the present article, we review the scientific literature on the risk of Facebook (over-)use. Addressing this topic is critical because evidence indicates the development of problematic Facebook use (“Facebook addiction”) due to excessive and uncontrolled use behavior with various psychological and physiological effects. We conducted a review to examine the scope, range, and nature of prior empirical research on the negative psychological and physiological effects of Facebook use. Our literature search process revealed a total of 232 papers showing that Facebook use is associated with eight major psychological effects (perceived anxiety, perceived depression, perceived loneliness, perceived eating disorders, perceived self-esteem, perceived life satisfaction, perceived insomnia, and perceived stress) and three physiological effects (physiological stress, human brain alteration, and affective experience state). The review also describes how Facebook use is associated with these effects and provides additional details on the reviewed literature, including research design, sample, age, and measures. Please note that the term “Facebook use” represents an umbrella term in the present work, and in the respective sections it will be made clear what kind of Facebook use is associated with a myriad of investigated psychological variables. Overall, findings indicate that certain kinds of Facebook use may come along with significant risks, both psychologically and physiologically. Based on our review, we also identify potential avenues for future research.