New technologies and innovations have often improved population well-being and societal function; however, these are also often initially accompanied by worry and fear. In some cases, such worries can impede, or even prevent entirely, the adoption of the technology. Mobile health (mHealth), a discipline broadly focused on employing ambulatory technologies to improve the affordability, reach, and effectiveness of health promotion and clinical intervention approaches, offers new innovations and opportunities. Despite emerging evidence supporting mHealth efficacy (eg, for improving health outcomes), some individuals have concerns about mHealth technology that may impede scalability, efficacy, and, ultimately, the public health benefits of mHealth. We present a review and conceptual framework to examine these issues, focusing on three overarching themes: biophysiological, psychological, and societal concerns. There are features of mHealth that lead to worries about the potential negative effects on an individual’s health (eg, due to exposure to electromagnetic or radio waves), despite evidence supporting the safety of these technologies. When present, such beliefs can lead to worry that gives rise to the experience of unpleasant and concerning physical symptoms—the nocebo effect. This may represent an important implementational barrier because of apprehension toward beneficial mHealth products (or features thereof, such as wireless charging, wearable or implantable sensors, etc) and may also have broader ramifications (eg, leading to economic, governmental, and legislative actions). In addition to reviewing evidence on these points, we provide a broad three-step model of implementation research in mHealth that focuses on understanding and preventing health concerns to facilitate the safe and effective scalability of mHealth (and that may be generalizable and applied to similar technologies):(1) evaluating and better discerning public perceptions and misperceptions (and how these may differ between populations),(2) developing theory-based public health communication strategies regarding the safety of mHealth, and (3) disseminating this messaging using evidence-based methods. Collectively, these steps converge on reviewing evidence regarding the potential role of worry and nocebo in mHealth and providing a model for understanding and changing attitudes and preventing unfounded negative perceptions related to mHealth technology.