There is a shortage of medical isotopes in the world today. Two of the most important isotope producing reactors, the National Research Universal (NRU) reactor in Canada and the High Flux Reactor (HFR) in the Netherlands, are currently under repair. The main consequence is that the supply of 99Mo, the workhorse isotope of nuclear medicine, is far below the medical demand. This demand comes from >30 million patients worldwide that are diagnosed each year using 99mTc, the daughter isotope of 99Mo. Supply shortages will remain the case until these two reactors are returned to service. However, both these reactors are close to 50 years old, as are the three other main isotope producing reactors (BR2, Belgium, OSIRIS, France and SAFARI, South Africa, Fig. 1). Since it is expected that the clinical demand for 99mTc will remain strong for decades to come [1, 2], the remaining life time of these reactors is too short. The future of a significant part of nuclear medicine is therefore dependent on new reactors being built, or on new technologies being developed. Fig. 1 The contribution of the five most important reactors to world 99Mo production In several countries, the present shortage has given rise to studies on possible ways to resolve the problem. In Canada, it was originally planned to replace the NRU by two so-called MAPLE reactors, but that project was discontinued for technical reasons [3]. Subsequently, at the initiative of the Canadian Government, an independent expert panel reviewed a large number of different proposals for 99Mo production, in order to advise on the way forward [4]. In the USA a committee investigated options to move away from the current use of highly enriched uranium (HEU) as target material for 99Mo production [5]. In the Netherlands, a new multipurpose reactor Pallas [6] has been proposed. This prompted the Dutch government to commission an independent review of all possibilities to produce 99Mo in the future [7]. Such an important issue as the production of 99Mo has political, economic and scientific aspects. In this editorial we focus on a scientific comparison of all the options, using the results of the independent committees as a basis. First we discuss the current technology of irradiating HEU plates in reactors. Then we describe the possible alternatives for 99Mo production in four broad categories: molybdenum targets in reactors, target plates in accelerators, 99Mo extraction from liquid reactors and the replacement of the HEU targets by low enriched uranium (LEU). Finally we present conclusions, which are supported by the independent reviews mentioned above.