Nanocrystals (NCs), an advanced nanotechnology-based drug delivery approach, gained major interest in pharmaceutical sciences because of their ability to improve the solubility and bioavailability of poorly water-soluble drugs. Regulatory considerations are essential to ensure the safety, effectiveness, and quality of NCs during the drug development and commercialization processes. These factors include characterization, processes for manufacturing, and developing relevant specifications. Because these variables substantially influence drug performance, regulatory bodies like the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) demand comprehensive physicochemical characterization of NCs, including particle size, surface area, and zeta potential. To achieve consistent product quality, manufacturing processes need to be well-controlled. The production of NCs also entails solving safety issues such as toxicity and immunogenicity, which might occur due to NCs’ small size and large surface area. Regulatory requirements also stress the significance of developing robust analytical techniques, bioequivalence studies, and stability testing to ensure product quality throughout its shelf life. This chapter first introduces the overview of the NCs. Further, we discussed the relevance of regulatory concerns in the design of NC-based formulations and key regulatory agency guidelines. In addition, we shed light on the clinical implications of NCs. Furthermore, we discussed the procedure for regulatory submissions as well as new developments in NC development.