BackgroundThe use of mobile health (mHealth) technologies to improve population-level health outcomes around the world has surged in the last decade. Research supports the use of mHealth apps to improve health outcomes such as maternal and infant mortality, treatment adherence, immunization rates, and prevention of communicable diseases. However, developing countries face significant barriers to successfully implement, sustain, and expand mHealth initiatives to improve the health of vulnerable populations.ObjectiveWe aimed to identify and synthesize barriers to the use of mHealth technologies such as text messaging (short message service [SMS]), calls, and apps to change and, where possible, improve the health behaviors and health outcomes of populations in developing countries.MethodsWe followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Deriving search criteria from the review’s primary objective, we searched PubMed and CINAHL using an exhaustive terms search (eg, mHealth, text messaging, and developing countries, with their respective Medical Subject Headings) limited by publication date, English language, and full text. At least two authors thoroughly reviewed each article’s abstract to verify the articles were germane to our objective. We then applied filters and conducted consensus meetings to confirm that the articles met the study criteria.ResultsReview of 2224 studies resulted in a final group of 30 articles for analysis. mHealth initiatives were used extensively worldwide for applications such as maternal health, prenatal care, infant care, HIV/AIDS prevention, treatment adherence, cardiovascular disease, diabetes, and health education. Studies were conducted in several developing countries in Africa, Asia, and Latin America. From each article, we recorded the specific health outcome that was improved, mHealth technology used, and barriers to the successful implementation of the intervention in a developing country. The most prominent health outcomes improved with mHealth were infectious diseases and maternal health, accounting for a combined 20/30 (67%) of the total studies in the analysis. The most frequent mHealth technology used was SMS, accounting for 18/30 (60%) of the studies. We identified 73 individual barriers and grouped them into 14 main categories. The top 3 barrier categories were infrastructure, lack of equipment, and technology gap, which together accounted for 28 individual barriers.ConclusionsThis systematic review shed light on the most prominent health outcomes that can be improved using mHealth technology interventions in developing countries. The barriers identified will provide leaders of future intervention projects a solid foundation for their design, thus increasing the chances for long-term success. We suggest that, to overcome the top three barriers, project leaders who wish to implement mHealth interventions must establish partnerships with local governments and nongovernmental organizations to secure funding, leadership, and the required infrastructure.