OBJECTIVES: To target patients with "personalized" interventions with the highest probability of success, understanding what works with other behaviors provides empirical guidance, as few outcomes are explicitly medication adherence-related. This study's purpose is to glean 1) the characteristics of individuals or interventions examined in “tailored” or “targeted” health communication interventions, and 2) the components or combination of successful strategies tailored to the individual's needs and targeted to the social groups in which the patient is embedded.   METHODS: A systematic review was conducted, with articles identified via searches in MEDLINE and Embase, using keywords representing individual, interventional, and behavioral factors. Inclusion criteria: published peer-reviewed articles in English, 2000-2012; 77 studies reflected behavioral outcomes (medication adherence, preventive screening, health promotion, and self-management of disease). The review specified individual factors (sociodemographic, behavioral, contextual, disease) as well as elements upon which interventions were customized (delivery, content, form, dose/frequency, setting, level of analysis). RESULTS: Across all outcomes assessed (n=133), 52.6% of tailored or targeted interventions demonstrated statistically significant benefit, with additional 12.8% effective (not statistically), 9.8% mixed, 24.8% non-significant. Regarding behaviors associated with multiple morbidities: most studies evidenced health promoting effects (medication adherence, 66.7%; diet/obesity, 65.9%; physical activity, 47.4%; screening, 71.4%). Disease-specific outcomes reflected stronger findings. Individual characteristics were clustered into groups for analysis, with significantly positive effects for 3 of 4 clusters: sociodemographic, 59.0%; behavioral, 63.4%, contextual, 52.6%.  Within group differences indicated support for specific factors within each cluster (age vs. education, barriers vs. self-efficacy). Effects were moderated by intervention-type (tailored vs tailored+targeted). CONCLUSIONS: A matrix developed for this review permits a refined approach to creating interventions focusing on the interaction ("person x intervention") features of effective strategies. Several candidate characteristics of patients to prioritize in medication adherence program development were identified, using evidenced-based selection of patient-centered strategies that appropriately match what has worked and for whom.