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Single photon emission computed tomography (SPECT) and positron emission tomography (PET) have their signature on paving the way to molecular diagnostics and personalized medicine. The former will be the topic of the current paper where the authors address the current position of the molecular SPECT imaging among other imaging techniques, describing strengths and weaknesses, differences between SPECT and PET, and focusing on different SPECT designs and detection systems. Radiopharmaceutical compounds of clinical as well-preclinical interest have also been reviewed. 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