Abstract The past decade has seen a dramatic increase in the number of Food and Drug Administration approval of oral anti-cancer drugs (OACDs). In 2018 alone, OACDs comprised ten of the sixteen newly approved oncology therapeutics in the United States. Despite the clinical benefits and convenience of OACDs, these new oral options present potential challenges, including polypharmacy, and can result in increased toxicities, drug–drug interactions (DDIs), inappropriate consumption of medications, and medication non-adherence. Adverse drug events have the potential to affect quality of life, healthcare utilization, treatment response, and survival. For the treatment of breast cancer, Endocrine therapies have remained a critical component of care for early stage and advance disease. Despite the proven efficacy adherence to therapy is suboptimal. Issues related to non-adherence are increasingly important, as analyses from prospective randomized trials show compliance to endocrine therapy is associated with improved disease-free survival. The reasons for non-adherence to hormonal therapy are multifactorial. Barriers to compliance include patient, physician, medication and system related variables and poor compliance is usually associated with a combination of these factors. Characteristics associated with non-adherence include very high and low age, minority race, being single, increased number of comorbidities, lack of knowledge about efficacy of AI therapy, history of non-adherence to other chronic medications, limited insurance status, and higher out of pocket costs. Side effects from hormonal therapy is the most common reason for early discontinuation. An understanding of factors that contribute to non-adherence and interventions that have been tested to improve adherence will be discussed. Medication compliance has become a more salient issue in cancer care with the increased availability of oral antineoplastic therapies for breast cancer. The treatment of BC now routinely encompasses targeted therapies such as oral poly(ADP-ribose) polymerase (PARP) inhibitors and cyclin-dependent kinase 4 (CDK4) and CDK6 inhibitors, PI3 Kinase(Pi3K) Inhibitors, in addition to traditional ET. Furthermore, as advances in BC treatment have improved long-term prognosis, the management of other chronic conditions has become an essential component of BC survivorship care. It remains unclear how this increased oral medication burden on BC survivors affects compliance with both ET and other chronic medications. Issues related to adherence measurement will be discussed. Citation Format: Dawn Hershman. How to measure and improve drug adherence in clinical trials [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr WS1-2.