Objective: To evaluate the impact of pharmaceutical care (PC) interventions on health-related quality of life (HRQoL) and determine sensitivity of HRQoL measures to PC services. Data Sources: MEDLINE, EMBASE, International Pharmaceutical Abstracts, PubMed, Global Health, PsychINFO, CINAHL, and Web of Science (January 2005 to September 2015) were searched. Study Selection and Data Extraction: Original English-language articles were included if PC impact on HRQoL was evaluated and reported using validated HRQoL measures. Data Synthesis: A total of 31 randomized controlled trials, 9 nonrandomized studies with comparison groups, and 8 before-after studies were included. PC interventions resulted in significant improvement in I domain and >= 3 domains of HRQoL measures in 66.7% and 27.1% of the studies, respectively. There was a significant improvement in at least I domain in 18 of 32 studies using generic and 16 of 21 studies using disease-specific measures. When the Short Form 36 Items Health Survey (SF-36) measure was used, PC interventions had a moderate impact on social functioning (standardized mean difference [SMD] = 0.59; 95% Cl = 0.14, 1.04), general health (SMD = 0.36; 95% CI = 0.12, 0.59), and physical functioning (SMD = 0.30; 95% Cl = 0.11, 0.48). The pooled data on heart failure-specific (SMD = -0.17; 95% CI = -0.43, 0.09), asthma-specific (SMD = 0.17; 95% CI = -0.03, 0.36), and chronic obstructive pulmonary disease specific (SMD = -0.09; 95% CI = -0.37, 0.19) measures indicated no significant impact of PC on HRQoL. Conclusions: PC interventions can significantly improve at least I domain of HRQoL. Existing measures may have minimal to moderate sensitivity to PC interventions, with evidence pointing more toward social functioning, general health, and physical functioning of the SF-36 measure. However, evidence generated from current non PC-specific HRQoL measures is insufficient to judge the impact of PC interventions on HRQoL. The development of a suitable HRQoL measure for PC interventions may help generate better evidence for the contribution of pharmacist services to improving HRQoL.