The feasibility of on-line production of short-lived radioactive isotopes was demonstrated already in 1951 by O. Kofoed Hansen and K.-O. Nielsen. They performed experiments on short-lived isotopes of noble gas elements that were produced by connecting a target, irradiated by protons, directly to an isotope separator.

ISOLDE, an acronym for Isotope Separator On Line DEvice, was originally proposed at the 600 MeV Proton Synchrocyclotron in 1964. The first experiments started there in 1967. ISOLDE underwent several upgrades until it was finally moved to the PSB in 1992. Amongst the existing facilities, ISOLDE presently offers worldwide a wide diversity of radioactive isotopes, and the installation of a post-accelerator at ISOLDE (REX-ISOLDE) has opened new fields of research with radioactive ion beams of higher energies. In this respect the facility is complementary to other European radioactive ion beam accelerators such as SPIRAL (GANIL, France) and GSI (Darmstadt, Germany), and provides a wider range of intense accelerated ions compared to HRIBF (Oak Ridge, USA) and ISAC (Vancouver, Canada).