Background: Unintentional medication nonadherence is common and has been associated with poor health outcomes and increased health care costs. Earlier research demonstrated a relationship between habit strength and medication adherence. Previous research also examined a habit's direct effect on adherence and how habit interacts with more conscious factors to influence or overrule them. However, the relationship between habit and adherence and the role of habit-based mobile health (mHealth) interventions remain unclear., Objective: This review aimed to systematically evaluate the most recent evidence for habit strength, medication adherence, and habit-based mHealth interventions across chronic medical conditions., Methods: A keyword search with combinations of the terms habit, habit strength, habit index, medication adherence, and medication compliance was conducted on the PubMed database. After duplicates were removed, two authors conducted independent abstract and full-text screening. The guidelines for the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were followed when reporting evidence across the included and reviewed studies., Results: Of the 687 records examined, 11 met the predefined inclusion criteria and were finalized for data extraction, grading, and synthesis. Most included studies (6/11, 55%) were cross-sectional and used a theoretical model (8/11, 73%). The majority of studies measured habit strength using the self-report habit index and self-report behavioral automaticity index (9/11, 82%). Habit strength was positively correlated with medication adherence in most studies (10/11, 91%). Habit mediated the effects of self-efficacy on medication adherence (1/11, 9%), and social norms moderated the effects of habit strength on medication adherence (1/11, 9%). Habit strength also moderated the effects of poor mental health symptoms and medication adherence (1/11, 9%). None of the included studies reported on using or proposing a habit-based mHealth behavioral intervention to promote medication adherence., Conclusions: Habit strength was strongly correlated with medication adherence, and stronger habit was associated with higher medication adherence rates, regardless of the theoretical model and/or guiding framework. Habit-based interventions should be used to increase medication adherence, and these interventions could leverage widely available mobile technology tools such as mobile apps or text messaging, and existing routines., (©Sherif M Badawy, Richa Shah, Usman Beg, Mallorie B Heneghan. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 28.04.2020.)