Objective: To examine the evidence regarding the effectiveness of medication reconciliation and review and to improve clinical outcomes in hospitals, the community, and aged care facilities. Data Source: This systematic review was undertaken in concordance with the PRISMA statement. Electronic databases, including MEDLINE, PsycINFO, EMBASE, and CINAHL were searched for relevant articles published between January 2000 and March 2014. Study Selection and Data Extraction: Randomized and nonrandomized studies rating the severity of medication discrepancies and medication-related problems identified during medication reconciliation and/or review were considered for inclusion. Data were extracted independently by 2 authors using a data collection form. Data Synthesis: Of the 5292 articles identified, 83 articles met the inclusion criteria. Medication reconciliation identified unintentional medication discrepancies in 3.4% to 98.2% of patients. There is limited evidence of the potential of these discrepancies to cause harm. Medication reviews identified medication-related problems or possible adverse drug reactions in 17.2% to 94.0% of patients. The studies reported conflicting findings regarding the impact of medication review on length of stays, readmissions, and mortality. Conclusions: The evidence demonstrates that medication reconciliation has the potential to identify many medication discrepancies and reduce potential harm, but the impact on clinical outcomes is less clear. Similarly, medication review can detect medication-related problems in many patients, but evidence of clinical impact is scant. Overall, there is limited evidence that medication reconciliation and medication review processes, as currently performed, significantly improve clinical outcomes, such as reductions in hospital readmissions.