Introduction: A rapid transition from a clinical-based classification to a pathology-based classification of neurodegenerative conditions, largely promoted by the increasing availability of imaging biomarkers, is emerging. The Framework for Innovative Multi-tracer molecular Brain Imaging, funded by the EU Joint Program - Neurodegenerative Disease Research 2016 “Working Groups for Harmonisation and Alignment in Brain Imaging Methods for Neurodegeneration,” aimed at providing a roadmap for the applications of established and new molecular imaging techniques in dementia. Methods: We consider current and future implications of adopting a pathology-based framework for the use and development of positron emission tomography techniques. Results: This approach will enhance efforts to understand the multifactorial etiology of Alzheimer's disease and other dementias. Discussion: The availability of pathology biomarkers will soon transform clinical and research practice. Crucially, a comprehensive understanding of strengths and caveats of these techniques will promote an informed use to take full advantage of these tools.