Suboptimal adherence to antiretroviral therapy (ART) is the most common cause of viral rebound. Accurate and reliable measures of ART adherence will be needed in the transition from reactive response to proactive prevention of viral rebound in the era of chronic human immunodeficiency virus (HIV) disease management. Such tools could define individual "signature adherence patterns," which could inform regimen choice and guide behavioral intervention. Upcoming advances in adherence monitoring present opportunities to better match HIV-disease treatment strategies with individual adherence behavior.