The New Drugs and Clinical Trials Rules (NDCTR), 2019, introduced by the Central Drugs Standard Control Organization (CDSCO), represent a transformative shift in India’s regulatory landscape for clinical research. This chapter provides a comprehensive review of the NDCTR, highlighting its structural framework, key provisions, and implications for stakeholders. The rules, comprising 13 chapters and 9 schedules, aim to streamline clinical trial processes, ensure participant safety, and promote ethical research practices. Key topics include the registration and functioning of ethics committees, regulatory pathways for clinical trials and bioavailability/bioequivalence studies, compensation mechanisms for trial-related injuries, and provisions for accelerated drug approvals in special circumstances. The chapter also discusses the import and manufacture of new drugs, including those not yet approved in India but required for life-threatening conditions. Recent amendments, such as deemed approvals and the registration of clinical research organizations, are also examined. This review serves as a practical guide for researchers, sponsors, and regulatory professionals navigating the evolving clinical trial environment in India.