Positron Emission Tomography (PET) is a diagnostic imaging procedure used regularly to acquire essential clinical information. The PET – CT hybrid, which consists of two scanning machines: PET scanner and an x-ray Computed Tomography (CT). At present these represent the technological hierarchy of Nuclear Medicine, occupying an important position in diagnostics. In fact, PET – CT has the capability to evaluate diseases through a simultaneous functional and morphostructural analysis. This allows for an earlier diagnosis of the disease state which is crucial for obtaining the required information to provide a more reliable prognosis and therapy. Presently, the most frequently used PET radiotracer [18F]fluorodeoxyglucose (FDG) has a major role in oncology. Useful information is being regularly obtained by using both FDG and a selection of radiotracer compounds to evaluate some of the most important biological processes. Thus, creating an opening for ‘Molecular Imaging’ and providing a platform for a potential revolution in the clinical diagnostic field. In this review, we hope to present the most interesting technicalogical and methodological advances in clinical diagnostics for oncology, neurology, and cardiology. A particular attention is dedicated to the applications of PET in neuropsychiatric diseases and its connections with receptor imaging.