The production of novel radionuclides is the first step towards the development of new effective radiopharmaceuticals, and the quality thereof directly affects the preclinical and clinical phases. In this review, novel radiometal production for medical applications is briefly elucidated. The production status of the imaging nuclide ⁴⁴Sc and the therapeutic β^--emitter nuclide ¹⁶¹Tb are compared to their more established counterparts, ⁶⁸Ga and ¹⁷⁷Lu according to their targetry, irradiation process, radiochemistry, and quality control aspects. The detailed discussion of these significant issues will help towards the future introduction of these promising radionuclides into drug manufacture for clinical application under Good Manufacturing Practice (GMP).