Background: Increased involvement of pharmacists in patient care may increase access to health care and improve patient outcomes. Purpose: To determine the effectiveness and harms of pharmacist-led chronic disease management for community-welling adults. Data Sources: MEDLINE, Cochrane Library, CINAHL, and International Pharmaceutical Abstracts from 1995 through February 2016, and reference lists of systematic reviews and included studies. Study Selection: 65 patient populations in 63 studies conducted in the United States of any design reported outcomes of pharmacist-led chronic disease management versus a comparator for community-dwelling adults in the United States. Studies set in retail pharmacies were excluded. Data Extraction: Data extraction done by a single investigator was confirmed by a second investigator; risk of bias was assessed by 2 investigators; and strength of evidence was determined by consensus. Data Synthesis: Pharmacist-led care was associated with similar numbers of office visits, urgent care or emergency department visits, and hospitalizations (moderate-strength evidence) and medication adherence (low-strength evidence) compared with usual care (typically continuing a prestudy visit schedule). Pharmacist-led care increased the number or dose of medications received and improved study-selected glycemic, blood pressure, and lipid goal attainment (moderate-strength evidence). Mortality and clinical events were similar (low-strength evidence). Evidence on patient satisfaction was mixed and insufficient. The reporting of harms was limited. Limitations: Interventions were heterogeneous. Studies were typically short-term and designed to assess physiologic intermediate outcomes rather than clinical events. Reporting of many clinical outcomes of interest was limited, and often they were not the study-defined primary end points. Conclusion: Pharmacist-led chronic disease management was associated with effects similar to those of usual care for resource utilization and may improve physiologic goal attainment. Further research is needed to determine whether increased medication utilization and goal attainment improve clinical outcomes. Primary Funding Source: Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Quality Enhancement Research Initiative.