We present a plug-and-play radiosynthesis platform and accompanying computer software based on modular subunits that can easily and flexibly be configured to implement a diverse range of radiosynthesis protocols. Modules were developed that perform: (i) reagent storage and delivery, (ii) evaporations and sealed reactions, and (iii) cartridge-based purifications. The reaction module incorporates a simple robotic mechanism that removes tubing from the vessel and replaces it with a stopper prior to sealed reactions, enabling the system to withstand high pressures and thus provide tremendous flexibility in choice of solvents and temperatures. Any number of modules can rapidly be connected together using only a few fluidic connections to implement a particular synthesis, and the resulting system is controlled in a semi-automated fashion by a single software interface. Radiosyntheses of 2-[(18)F]fluoro-2-deoxy-d-glucose ([(18)F]FDG), 1-[(18)F]fluoro-4-nitrobenzene ([(18)F]FNB), and 2 -deoxy-2 -[(18)F]fluoro-1-β-d-arabinofuranosyl cytosine (d-[(18)F]FAC) were performed to validate the system and demonstrate its versatility.