Exercise is widely recognized as a critical component of a healthy lifestyle by multiple scientific and regulatory bodies. Yet only 35% of adults in the United States even report engaging in regular physical activity. In response to this challenge, the Exercise is Medicine (EIM) initiative encourages clinicians in all settings to regularly assess and counsel patients on physical activity in an attempt to reduce levels of inactivity. The purpose of this article is to highlight key challenges to the implementation of the EIM initiative to promote physical activity and to identify potential opportunities to overcome these challenges. EIM is a global health initiative that endorses "exercise" to be a "vital sign" in all clinical settings. Specifically to assess and compare the patient's physical activity level to national guidelines for physical activity and then promote discussions or referrals based on results. Since its 2007 launch, advocates of the EIM initiative have increased global awareness to promote the EIM mission of integrating and implementing physical activity into healthcare systems, local communities, and individuals' daily lives. Physical activity is fundamental to the overall health of all people across all geographic locations and throughout the lifespan. Promoting physical activity as a healthy lifestyle change has specific challenges but necessary to decrease health disparities related to inactivity.