The exchange and use of health information can help healthcare professionals and policymakers make informed decisions on ways of improving patient and population health. Many low- and middle-income countries (LMICs) have however failed to embrace the approaches and technologies to facilitate health information exchange (HIE). We sought to understand the barriers and facilitators to the implementation and adoption of HIE in LMICs. Two reviewers independently searched 11 academic databases for published and on-going qualitative, quantitative and mixed-method studies and searched for unpublished work through the Google search engine. The searches covered the period from January 1990 to July 2014 and were not restricted by language. Eligible studies were independently, critically appraised and then thematically analysed. The searches yielded 5461 citations after de-duplication of results. Of these, 56 articles, three conference abstracts and four technical reports met the inclusion criteria. The lack of importance given to data in decision making, corruption and insecurity, lack of training and poor infrastructure were considered to be major challenges to implementing HIE, but strong leadership and clear policy direction coupled with the financial support to acquire essential technology, improve the communication network, and provide training for staff all helped to promote implementation. The body of work also highlighted how implementers of HIE needed to take into account local needs to ensure that stakeholders saw HIE as relevant and advantageous. HIE interventions implemented through leapfrog technologies such as telehealth/telemedicine and mHealth in Brazil, Kenya, and South Africa, provided successful examples of exchanging health information in LMICs despite limited resources and capability. It is important that implementation of HIE is aligned with national priorities and local needs.