Abstract: Using molecular imaging techniques, radionuclide-labeled molecular probes can provide noninvasive and real-time visualization of specific biochemical processes in the living humans and pathological process of various human diseases at the molecular level, which will pave the way to precision medicine. ^99mTc-radiopharmaceuticals is playing significant roles in the diagnosis of human diseases and efficacy monitoring of therapeutic strategies together with single photon emission computed tomography imaging modality. This review provided an overview of current status of ^99mTc-radiopharmaceuticals used in clinic and clinical trials. Possible future trends in the field of ^99mTc-radiopharmaceuticals were discussed. Investigation on the new targets or new biochemical processes as targets and basic technetium chemistry including exploring novel labeling methods and novel technetium building blocks were addressed. Development on the novel ^99mTc-radiopharmaceuticals with high affinity, selectivity and specificity for the imaging of unique targets or specific biochemical processes together with ^99mTc-labeling methods suitable for clinical use will accelerate the clinical translation of new ^99mTc-radiopharmaceuticals.