Molecular imaging using positron emission tomography (PET) has become a major biomedical imaging technology. Its application towards characterisation of biochemical processes in disease could enable early detection and diagnosis, development of novel therapies and treatment evaluation. The technology is underpinned by the use of chemical probes radiolabelled with short-lived positron-emitting radioisotopes which can be designed to be specific and selective for biological targets in vivo e.g., receptors, protein deposits, enzymes, and metabolism. My talk will focus on their development, the translational steps, and their application to clinical PET imaging research into neurodegenerative diseases to delineate and understand the various pathological components of these disorders.