Abstract During the past decade, the number of studies describing nanostructured lipid carriers (NLCs)-based formulations has been dramatically increased. The raise in NLC exploitation is essentially due to defeated barriers within the technological process of lipid-based nanoparticles’ formulation and increased knowledge of the underlying mechanisms of transport of NLCs via different routes of administration. This review article aims to give an overview on the current state of the art of NLC as controlled drug delivery systems for future clinics through novel NLC applications providing examples of successfull outcomes. The reported data clearly illustrate the promise of these nanoparticles for novel treatments in the near future. From the Clinical Editor The understanding of the nanostructured lipid carriers (NLC)-based formulations has improved with continuing research recently. The result has seen an increase in the use of these in the clinical setting. In this comprehensive review, the authors discussed the current state and major challenges in the use of nanostructured lipid carriers as controlled drug delivery systems.