The authors conducted a systematic review of the published literature on social media use in medical education to answer two questions: (1) How have interventions using social media tools affected outcomes of satisfaction, knowledge, attitudes, and skills for physicians and physicians-in-training? and (2) What challenges and opportunities specific to social media have educators encountered in implementing these interventions? The authors searched the MEDLINE, CINAHL, ERIC, Embase, PsycINFO, ProQuest, Cochrane Library, Web of Science, and Scopus databases (from the start of each through September 12, 2011) using keywords related to social media and medical education. Two authors independently reviewed the search results to select peer-reviewed, English-language articles discussing social media use in educational interventions at any level of physician training. They assessed study quality using the Medical Education Research Study Quality Instrument. Fourteen studies met inclusion criteria. Interventions using social media tools were associated with improved knowledge (e.g., exam scores), attitudes (e.g., empathy), and skills (e.g., reflective writing). The most commonly reported opportunities related to incorporating social media tools were promoting learner engagement (71% of studies), feedback (57%), and collaboration and professional development (both 36%). The most commonly cited challenges were technical issues (43%), variable learner participation (43%), and privacy/security concerns (29%). Studies were generally of low to moderate quality; there was only one randomized controlled trial. Social media use in medical education is an emerging field of scholarship that merits further investigation. Educators face challenges in adapting new technologies, but they also have opportunities for innovation.