Master Protocols are typically categorized into two types: basket protocols and umbrella protocols. Basket protocols typically evaluate one or more therapies across different disease category or type and umbrella protocols evaluate multiple therapies within the same disease category or type. Both types of master protocols have been initiated within the NCTN in the last 5 years. As these types of protocols are relatively new, researchers are continuing to develop the best practices for the design, conduct, and monitoring of such protocols. Examples of such studies launched within the NCTN are the Lung-MAP trial, NCI-MATCH, the DART trial, and the ALCHEMIST trial. The Lung-MAP master protocol, which launched in 2014, is designed to evaluate biomarker-driven therapies in biomarker-defined subgroups of advanced, previously-treated non-small cell lung cancer (NSCLC). The ALCHEMIST trial, also launched in 2014, is also designed to evaluate biomarker-driven therapies in NSCLC, but in the adjuvant setting. The NCI-MATCH trial, launched in 2015, is designed to evaluate biomarker-driven therapies within biomarker-defined subgroups across multiple histologic types of cancers. The DART trial (Dual Anti–CTLA-4 and Anti–PD-1 Blockade in Rare Tumors), launched in 2017, is designed to evaluate a combination of two immunotherapy agents (nivolumab and ipilimumab) in cohorts of patients with rare tumor types. This handful of studies launched within the NCTN highlight the possible variations in types of master protocols and that there isn’t a uniform basket or umbrella design. The considerations for monitoring of master protocols depends on the type of protocol design, phase of study, amount of information known about the investigational therapy and the disease setting in which it is being evaluated. In this talk, I will discuss the monitoring considerations for these types of trials conducted within the NCTN.