Cyclotron radioisotope production has a long and successful history. Starting in 1955, liquid and gaseous targets were the backbone of the first era of PET imaging and were used to produce a large number of radiopharmaceuticals. Throughout the past century, fluorine-18 and carbon-11 have been the most commonly produced radioisotopes using cyclotrons due to their multiple applications and the growing demand for radiopharmaceuticals, e.g., [18F]FDG in the oncological diagnostic field. Carbon-11 was one of the pillars where nuclear medicine started, in particular in the fields of neurology and oncology, where many radiopharmaceuticals have helped the development of molecular imaging. In the past 10 years, radioisotope demand has shown multiple trends. Carbon-11 demand collapsed for multiple reasons, one of them being the replacement of carbon-11 radiopharmaceuticals with fluorine-18 analogues. Fluorine-18 requests continue to grow, but, at the same time, requests for cyclotron radiometal production have become a priority due to new theragnostic applications. These scenarios open up more challenging isotope productions and focus not only on fluorine-18 target improvement but also on solid/liquid cyclotron target developments for radiometal production.