CONTEXT: Clinical trials are necessary to improve the health care of children, but only one-quarter are conducted in the low- to middle-income countries (LMICs) in which 98% of the global burden of disease resides. OBJECTIVE: To describe stakeholder beliefs and experiences of conducting trials in children in LMICs. DATA SOURCES: Electronic databases were searched to August 2014. STUDY SELECTION: Qualitative studies of stakeholder perspectives on conducting clinical trials among children in LMICs. DATA EXTRACTION: Findingswere analyzed by using thematic synthesis. RESULTS: Thirty-nine studies involving 3110 participants (children [n = 290], parents or caregivers [n = 1609], community representatives [n = 621], clinical or research team members [n = 376], regulators [n = 18], or sponsors [n = 15]) across 22 countries were included. Five themes were identified: centrality of community engagement (mobilizing community, representatives' pivotal role, managing expectations, and retaining involvement); cognizance of vulnerability and poverty (therapeutic opportunity and medical mistrust); contending with power differentials (exploitation, stigmatization, and disempowerment); translating research to local context (cultural beliefs, impoverishment constraints, and ethical pluralism); and advocating fair distribution of benefits (health care, sponsor obligation, and collateral community benefits). LIMITATIONS: Studies not published in English were excluded. CONCLUSIONS: Conducting trials in children in LMICs is complex due to social disadvantage, economic scarcity, idiosyncratic cultural beliefs, and historical disempowerment, all of which contribute to inequity, mistrust, and fears of exploitation. Effective community engagement in recruiting, building research capacities, and designing trials that are pragmatic, ethical, and relevant to the health care needs of children in LMICs may help to improve the equity and health outcomes of this vulnerable population.