OBJECTIVES: To assess the range and focus of health research that has involved interactive internet and mobile technology (“social media”; SM). METHODS: We conducted a systematic review of studies that investigated the use of SM, or used SM as a research tool, published in English since 2003 and indexed in MEDLINE and EMBASE. RESULTS: We identified 3,773 unique studies, of which 304 reported primary research or were systematic reviews of such studies. Of these, 192 (63%) were surveys of actual or potential users of SM, including healthcare professionals (20%), patients with a specific disease or problem (46%), or the general public (34%); 40 (13%) were articles describing SM tools or sites; 71 (23%) assessed the potential of SM to increase knowledge or improve clinical outcomes, of which 22 compared SM with more traditional support or information; 71 (23%) described SM users; 53 (17%) sought their views on the benefits of SM; 24 (8%) discussed the potential harm its use could do to professional-patient relationships; and 25 (8%) analysed SM content. SM were also used as a tool to recruit participants into research (85 articles, 28%), especially on topics such as sexual practices, intimate partner violence, or substance abuse, or involving groups typically underrepresented in clinical research.  Of the various types of SM studied or used to recruit participants into research, Facebook was cited in 73 articles (24%); mobile apps in 40 papers (13%); PatientsLikeMe and Twitter in 13 articles (4%) each; MySpace in 3 articles (1%); and other online forums in 70 articles (23%). CONCLUSIONS: SM is a rich source of data on patients and healthcare professionals. It may be particularly useful in targeting patients with rare diseases, and studying attitudes and behaviours relating to taboo subjects. SM may also increase recruitment into research studies, especially from hard-to-reach groups.