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Key Points Question What are the health system factors that support or impair the ability of nonphysician health workers to treat noncommunicable diseases in low- and middle-income countries? Findings This systematic review and qualitative analysis examined 15 systematic reviews, encompassing 71 studies. These studies consistently demonstrated 6 key lessons of successful care by nonphysician health workers: careful staff recruitment, detailed training, authorization to provide autonomous care, adequate medications and supplies, reliable data systems, and fair, performance-based compensation. Meaning Effective, scalable care for noncommunicable diseases led by nonphysicians is feasible in diverse low-resource settings but requires several common, key implementation steps., This systematic review and qualitative analysis examines the health system barriers to and facilitators of care for noncommunicable diseases by nonphysician health workers in low- and middle-income countries., Importance Cardiovascular disease, cancer, and other noncommunicable diseases (NCDs) are the leading causes of mortality in low- and middle-income countries. Previous studies show that nonphysician health workers (NPHWs), including nurses and volunteers, can provide effective diagnosis and treatment of NCDs. However, the factors that facilitate and impair these programs are incompletely understood. Objective To identify health system barriers to and facilitators of NPHW-led care for NCDs in low- and middle-income countries. Data Sources All systematic reviews in PubMed published by May 1, 2018. Study Selection The search terms used for this analysis included “task shifting” and “non-physician clinician.” Only reviews of NPHW care that occurred entirely or mostly in low- and middle-income countries and focused entirely or mostly on NCDs were included. All studies cited within each systematic review that cited health system barriers to and facilitators of NPHW care were reviewed. Data Extraction and Synthesis Assessment of study eligibility was performed by 1 reviewer and rechecked by another. The 2 reviewers extracted all data. Reviews were performed from November 2017 to July 2018. All analyses were descriptive. Main Outcomes and Measures All barriers and facilitators mentioned in all studies were tallied and sorted according to the World Health Organization’s 6 building blocks for health systems. Results This systematic review and qualitative analysis identified 15 review articles, which cited 156 studies, of which 71 referenced barriers to and facilitators of care. The results suggest 6 key lessons: (1) select qualified NPHWs embedded within the community they serve; (2) provide detailed, ongoing training and supervision; (3) authorize NPHWs to prescribe medication and render autonomous care; (4) equip NPHWs with reliable systems to track patient data; (5) furnish NPHWs consistently with medications and supplies; and (6) compensate NPHWs adequately commensurate with their roles. Conclusions and Relevance Although the health system barriers to NPHW screening, treatment, and control of NCDs and their risk factors are numerous and complex, a diverse set of care models has demonstrated strategies to address nearly all of these challenges. These facilitating approaches—which relate chiefly to strong, consistent NPHW training, guidance, and logistical support—generate a blueprint for the creation and scale-up of such programs adaptable across multiple chronic diseases, including in high-income countries.