While positron emission tomography (PET) represents the most advanced methodology using radiotracers, it is subject to two main constraints. The first is the physical accuracy with which the regional distribution, time course and concentration of the tracer can be determined. This is principally a function of the instrumentation. The second constraint is the biological accuracy, that a chosen tracer molecule defines the specific biological pathway under study. This paper discusses the application of PET, mainly to the brain, and future possible improvements to this powerful technique.