Positron emission tomography (PET) was developed in the seventies of the last century with the first commercial scanner becoming available in 1978. Originally, this novel tomographic imaging technique was seen and used as a quantitative method for measuring human physiological and pathophysiological processes at regional level. The two most important characteristics of PET were its quantitative nature and its extremely high sensitivity, which allowed measurements down to picomolar level. Over the following 10–20 years the molecular processes that could be investigated using PET expanded rapidly, ranging from perfusion through metabolism, preand post-synaptic receptor density and affinity, neurotransmitter release, and enzyme activity, to drug delivery and uptake. Given that PET, as mentioned, was characterised by two unique features (quantification and sensitivity), it is of interest to note that by the turn of the century one of them, sensitivity, was starting to be applied in clinical medicine, in particular its sensitivity to detect (distant) metastases using F-FDG. This led to a significant improvement in staging, which had direct consequences with regard to the choice of appropriate therapy (e.g. avoidance of futile surgery). As a result PET became the fastest growing medical technology, which was in sharp contrast to the situation in the mid-nineties, when the field (and the manufacturing industry) had been struggling to survive. Clearly, to detect metastases (by finding hot spots), quantification was not necessary, as the purpose of a PET staging study is simply to establish whether they are there or not. In addition, it was convenient that scanning could be performed according to a protocol that is standard in clinical nuclear medicine practice, i.e. inject the tracer, wait for sufficient uptake in tissue and finally position and scan the patient. For F-FDG, this waiting period is 1 h and, from the perspective of patient throughput, it is very convenient that the scanner is not occupied during this uptake period. It is unfortunate and somewhat ironic, however, that one of the unique characteristics of PET (sensitivity) has indirectly been the reason why the other (quantification) is less recognised and indeed unknown to many clinicians who became familiar with PET through staging studies, in which quantification is not required. On the basis of its success in staging, however, PET is now seen as a very promising technique for monitoring and even predicting response to therapy. Indeed, F-FDG PET is already used as a surrogate endpoint in the development of new anticancer drugs. In addition, other more specific tracers are increasingly being used in drug development, both in oncology and in neurology. In this context, it is very tempting to implement the same methodology that is used in F-FDG staging studies, i.e. the application of a static or whole-body protocol at some time after injection of the tracer. It should be noted that there are many aspects to quantification that need to be taken into account, i.e. scanner, physics and patient-related factors [1]. A prerequisite for quantification is that the scanner be equipped with accurate randoms, scatter and attenuation correction procedures. This may seem trivial, but it is well-known that the most recent scanners (i.e. PET/MRI) are associated with substantial errors in attenuation correction, even in the Color figures online at http://link.springer.com/article/10.1007/ s40336-014-0074-y