Background There is currently a lack of information about the uses, benefits, and limitations of social media for health communication among the general public, patients, and health professionals from primary research. Objective To review the current published literature to identify the uses, benefits, and limitations of social media for health communication among the general public, patients, and health professionals, and identify current gaps in the literature to provide recommendations for future health communication research. Methods This paper is a review using a systematic approach. A systematic search of the literature was conducted using nine electronic databases and manual searches to locate peer-reviewed studies published between January 2002 and February 2012. Results The search identified 98 original research studies that included the uses, benefits, and/or limitations of social media for health communication among the general public, patients, and health professionals. The methodological quality of the studies assessed using the Downs and Black instrument was low; this was mainly due to the fact that the vast majority of the studies in this review included limited methodologies and was mainly exploratory and descriptive in nature. Seven main uses of social media for health communication were identified, including focusing on increasing interactions with others, and facilitating, sharing, and obtaining health messages. The six key overarching benefits were identified as (1) increased interactions with others, (2) more available, shared, and tailored information, (3) increased accessibility and widening access to health information, (4) peer/social/emotional support, (5) public health surveillance, and (6) potential to influence health policy. Twelve limitations were identified, primarily consisting of quality concerns and lack of reliability, confidentiality, and privacy. Conclusions Social media brings a new dimension to health care as it offers a medium to be used by the public, patients, and health professionals to communicate about health issues with the possibility of potentially improving health outcomes. Social media is a powerful tool, which offers collaboration between users and is a social interaction mechanism for a range of individuals. Although there are several benefits to the use of social media for health communication, the information exchanged needs to be monitored for quality and reliability, and the users’ confidentiality and privacy need to be maintained. Eight gaps in the literature and key recommendations for future health communication research were provided. Examples of these recommendations include the need to determine the relative effectiveness of different types of social media for health communication using randomized control trials and to explore potential mechanisms for monitoring and enhancing the quality and reliability of health communication using social media. Further robust and comprehensive evaluation and review, using a range of methodologies, are required to establish whether social media improves health communication practice both in the short and long terms.