Also in 2021/2022, considerable efforts were invested into advancing human sports drug testing programs, recognizing and taking into account existing as well as emerging challenges in anti-doping, especially with regard to substances and methods of doping specified in the World Anti-Doping Agency's 2022 Prohibited List. In this edition of the annual banned-substance review, literature on recent developments published between October 2021 and September 2022 is summarized and discussed. Focus is put particularly on enhanced analytical approaches and complementary testing options in human doping controls, appreciating the exigence and mission in anti-doping and, equally, the contemporary "new normal" considering, for example, the athlete's exposome versus analytical sensitivity and applicable anti-doping regulations for result interpretation and management.