Along with the remarkable advancements in antiretroviral therapy (ART), new paradigms have emerged on the importance of adherence. Early studies with older antiretrovirals (ARVs) proposed that >95% adherence was required to achieve and maintain virologic suppression, which led to the concept that an undetectable HIV viral load (VL) was equivalent to full adherence. However, the potency and favorable pharmacology of the new ARVs have allowed for more forgiveness to missed doses, with recent studies demonstrating that the “minimal” level of ART adherence required to sustain viral suppression may range between 80-85% (and as low as 75%). While advantageous, achieving viral suppression despite variable ART adherence has de-emphasized the focus on adherence in clinical practice, limiting our understanding of its consequences at the individual (i.e., biological, virological) and population (i.e., transmission) levels. This is essential to maximizing the benefit of ART and controlling the HIV epidemic, since maintaining an undetectable HIV VL (mainly driven by adherence) is indispensable for the U=U (Undetectable=Untransmittable) strategy to be effective, and because adherence remains a lifelong challenge. However, despite its critical importance, we currently lack a gold-standard measure to quantify ART adherence. In response to this gap, several innovative methods and strategies to objectively measure ART adherence have emerged in recent years. These include: a) pharmacologic methods that inform about cumulative adherence and recent dosing by quantifying drug concentrations in plasma, urine, hair and dried blood spots; b) advances in electronic medication dispensers that monitor pill-taking behavior, and; c) digital pills that confirm medication ingestion. These novel methods have proven more accurate than self-report, can predict adverse clinical outcomes (i.e., viremia), and provide real-time adherence information that can lead to actionable interventions during a routine clinical visit. Moreover, pharmacologic methods can assess inter-individual pharmacokinetic differences not captured by HIV VL monitoring or other adherence measures. This symposium talk will address these and other questions by exploring the benefits and potential risks of forgiveness of modern ARVs (including long-acting agents), evaluating the pearls and pitfalls of existing and new ART adherence measures, and providing the audience with some practical strategies for integrating these tools into clinical practice.