Developments throughout the history of nuclear medicine have involved improvements in both instrumentation and radionuclides, which have been intertwined. Instrumentation developments always occurred during the search to improving devices' sensitivity and included advances in detector technology (with the introduction of cadmium zinc telluride and digital Positron Emission Tomography-PET-devices with silicon photomultipliers), design (total body PET) and configuration (ring-shaped, Single-Photon Emission Computed Tomography (SPECT), Compton camera). In the field of radionuclide development, we observed the continual changing of clinically used radionuclides, which is sometimes influenced by instrumentation technology but also driven by availability, patient safety and clinical questions. Some areas, such as tumour imaging, have faced challenges when changing radionuclides based on availability, when this produced undesirable clinical findings with the introduction of unclear focal uptakes and unspecific uptakes. On the other end of spectrum, further developments of PET technology have seen a resurgence in its use in nuclear cardiology, with rubidium-82 from strontium-82/rubidium-82 generators being the radionuclide of choice, moving away from SPECT nuclides thallium-201 and technetium-99m. These continuing improvements in both instrumentation and radionuclide development have helped the growth of nuclear medicine and its importance in the ever-evolving range of patient care options.