This manuscript provides a concise overview of the extensive research conducted by Bodor and collaborators over the past four decades concerning the application of cyclodextrin complexes in formulating drugs with challenging physicochemical characteristics for clinical use. Specifically, it emphasizes the utilization of 2-hydroxypropyl-β-cyclodextrin (HPβCD) to enhance the solubility and stability of chemical delivery systems (CDSs) designed in accordance with general retrometabolic drug design strategies, which were also pioneered by Bodor and associates. Furthermore, the paper discusses the development of an innovative HPβCD-based formulation comprising a dual cyclodextrin complex, which consist of a combination of inclusion and non-inclusion complexes, and led to the successful introduction and regulatory approval of cladribine oral tablets. The resultant Mavenclad tablets represent a clinically validated, safe, and effective oral therapeutic option for multiple sclerosis that is used worldwide surpassing sales of one billion US dollars in 2023 reaching blockbuster status.