Bipolar disorder is a chronic, progressive illness characterized by recurrent episodes of mania and depression. Self-report scales have historically played a significant role in the monitoring of bipolar symptoms. However, these tools rely on episodic memory, which can be unreliable and do not allow the clinician to monitor brief episodic symptoms or the course of symptoms over shorter periods of time. Mobile app-based questionnaires have been suggested as a tool to improve monitoring of patients with bipolar disorder. This paper aims to determine the feasibility and validity of mobile app-based self-report questionnaires. We performed a systematic review of the literature according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The PubMed, PsycInfo, Web of Science, Ovid MEDLINE, and EMBASE databases were searched for papers published in English that assessed adherence to and the validity of mobile app-based self-report questionnaires. Relevant studies published from database creation to May 22, 2020, were identified, and results examining the validity of and rates of adherence to app-based self-report questionnaires are reported. A total of 13 records were identified for inclusion in this review. Of these studies, 4 assessed the concurrent validity of mobile app-based self-report tools, with the majority of findings indicating significant associations between data collected using these tools and the Young Mania Rating Scale, Hamilton Depression Rating Scale-17, or Montgomery-Åsberg Depression Rating Scale (P<.001 to P=.24). Three studies comparing the variability or range of symptoms between patients with bipolar disorder and healthy controls suggested that these data are capable of differentiating between known groups. Two studies demonstrated statistically significant associations between data collected via mobile app-based self-report tools and instruments assessing other clinically important factors. Adherence rates varied across the studies examined. However, good adherence rates (>70%) were observed in all but 1 study using a once-daily assessment. There was a wide range of adherence rates observed in studies using twice-daily assessments (42%-95%). These findings suggest that mobile app-based self-report tools are valid in the assessment of symptoms of mania and depression in euthymic patients with bipolar disorder. Data collected using these tools appear to differ between patients with bipolar disorder and healthy controls and are significantly associated with other clinically important measures. It is unclear at this time whether these tools can be used to detect acute episodes of mania or depression in patients with bipolar disorder. Adherence data indicate that patients with bipolar disorder show good adherence to self-report assessments administered daily for the duration of the study periods evaluated. ©Eric C Chan, Yuting Sun, Katherine J Aitchison, Sudhakar Sivapalan. Originally published in JMIR Formative Research (http://formative.jmir.org), 08.01.2021.