BackgroundAssessment for mental health is performed by experts using interview techniques, questionnaires, and test batteries and following standardized manuals; however, there would be myriad benefits if behavioral correlates could predict mental health and be used for population screening or prevalence estimations. A variety of digital sources of data (eg, online search data and social media posts) have been previously proposed as candidates for digital biomarkers in the context of mental health. Playing games on computers, gaming consoles, or mobile devices (ie, digital gaming) has become a leading leisure activity of choice and yields rich data from a variety of sources.ObjectiveIn this paper, we argue that game-based data from commercial off-the-shelf games have the potential to be used as a digital biomarker to assess and model mental health and health decline. Although there is great potential in games developed specifically for mental health assessment (eg, Sea Hero Quest), we focus on data gathered “in-the-wild” from playing commercial off-the-shelf games designed primarily for entertainment.MethodsWe argue that the activity traces left behind by natural interactions with digital games can be modeled using computational approaches for big data. To support our argument, we present an investigation of existing data sources, a categorization of observable traits from game data, and examples of potentially useful game-based digital biomarkers derived from activity traces.ResultsOur investigation reveals different types of data that are generated from play and the sources from which these data can be accessed. Based on these insights, we describe five categories of digital biomarkers that can be derived from game-based data, including behavior, cognitive performance, motor performance, social behavior, and affect. For each type of biomarker, we describe the data type, the game-based sources from which it can be derived, its importance for mental health modeling, and any existing statistical associations with mental health that have been demonstrated in prior work. We end with a discussion on the limitations and potential of data from commercial off-the-shelf games for use as a digital biomarker of mental health.ConclusionsWhen people play commercial digital games, they produce significant volumes of high-resolution data that are not only related to play frequency, but also include performance data reflecting low-level cognitive and motor processing; text-based data that are indicative of the affective state; social data that reveal networks of relationships; content choice data that imply preferred genres; and contextual data that divulge where, when, and with whom the players are playing. These data provide a source for digital biomarkers that may indicate mental health. Produced by engaged human behavior, game data have the potential to be leveraged for population screening or prevalence estimations, leading to at-scale, nonintrusive assessment of mental health.