In neurodegenerative diseases, positron emission tomography (PET) imaging plays an important role in the early identification and differential diagnosis in particular in clinically challenging patients.¹⁸F-FDG is still the most widely used and established tracer in this patient group, with different cortical and subcortical regions being preferentially affected in different neurodegenerative diseases, such as frontotemporal dementia, Alzheimer's disease or Lewy Body dementia, resulting in typical hypometabolic patterns. Over the last decades, however, the implementation of tracers specific for the pathological deposits characteristic of the different diseases, such as amyloid and tau, has revolutionized the way of classifying and reporting cases of cognitive impairment of neurodegenerative origin, providing complementary information to¹⁸F-FDG PET. In neuro-oncology, PET imaging can be performed in several clinical indications, as highlighted in the joint European Association of Nuclear Medicine (EANM)/European Association of Neuro-Oncology (EANO)/Response assessment in neuro-oncology (RANO) practice guidelines on imaging in neuro-oncology. For assessment of glioma, amino-acid analogues, such as¹¹C-methionine or¹⁸F-FET, are used whenever clinically available, as they offer excellent tumor-to-background ratios in malignant tumors. Moreover, dynamic acquisition of amino-acid analogue tracers and assessment of the shape of the time-activity curve can be used to perform noninvasive grading of brain gliomas, differentiating low from high grade presentations. In both settings, however, thorough knowledge of the normal physiological tracer distribution and the variants and pitfalls that can occur during image acquisition, processing and interpretation is mandatory in order to provide optimal diagnostic information to referring physicians and patients. Especially in neuro-oncology, this process can be aided by the active use of coregistered magnetic resonance imaging to accurately identify the imaging correlates of developmental origin, acute and chronic stroke, inflammation, infection and seizure related activity.