Growing evidence documents that the influence of sedentary behaviors on brain health is not universally beneficial or detrimental but rather context-dependent and nuanced. More specifically, recent findings suggest that mentally active sedentary behavior, such as video gaming, may benefit brain health, whereas mentally passive sedentary behavior, such as television viewing, may not convey such benefits. However, traditional classification approaches do not fully recognize the importance of content relevance. In this opinion article, we propose a neurobiological, dual-axis framework combining mental activation and content relevance to distinguish effects of specific sedentary behavior types on brain health-related outcomes. This refined sedentary behavior taxonomy may open novel perspectives to clarify mechanisms and the roles of key moderators (e.g., age and life context) in future brain health research for enhanced public health strategies and more personalized lifestyle recommendations.