Natural killer (NK) cells have emerged as key players in cancer immunotherapy, offering promising therapeutic potential due to their innate ability to target and destroy malignant cells. This chapter focuses on the clinical translation of NK cells, providing an overview of their historical and current use in the clinic. We examine the regulatory framework for NK cell therapies in both the European Union and the United States of America, highlighting key differences and requirements for clinical application. The history of the use of NK cells in clinical trials is reviewed, tracing the progress from early studies to current cutting-edge trials aimed at harnessing the efficacy of NK cells against various cancers and in the treatment of autoimmune diseases. In addition, the technological challenges in the preparation and clinical manufacturing of NK cells are addressed, focusing on process development, characterization, and quality control. By examining these critical aspects, we aim to provide insights into the successful translation of NK cell therapies from research to clinical practice, paving the way for future innovations in immunotherapy.