Nuclear medicine relies on two main imaging modalities: single photon emission computed tomography (SPECT) and positron emission tomography (PET). Radiopharmaceuticals (or radiotracers) are the blood stream of nuclear medicine for the diagnosis or therapy of diseases. Diagnostic radiotracers that are small molecules labelled with a gamma-emitter for SPECT or positron-emitter for PET provide a non-invasive method to assess the disease or disease states and monitor the therapeutic efficacy of a specific treatment regime. Over the past four decades, radiopharmaceutical research has been practising one-pot synthesis at the tracer level (10(-7)-10(-6) M). Many (99m)Tc radiotracers currently used in nuclear medicine are routinely prepared by following the basic principles of one-pot synthesis. Unlike traditional organic one-pot synthesis, which often involves the formation of multiple C-C and C-heteroatom bonds in a single step, the (99m)Tc-centered one-pot synthesis requires the formation of multiple coordination bonds between Tc and various donor atoms, such as N, O, S and P. This review will illustrate how the (99m)Tc-centered one-pot synthesis is utilized for routine preparations of different (99m)Tc radiotracers.