The translocator protein (18 kDa) (TSPO), formerly known as the peripheral benzodiazepine receptor (PBR), was originally identified as an alternate binding site for the central benzodiazepine receptor (CBR) ligand, diazepam, in the periphery, but has now been distinguished as a novel site. The TSPO is ubiquitously expressed in peripheral tissues but only minimally in the healthy brain and increased levels of TSPO expression have been noted in neuroinflammatory conditions such as Alzheimer's disease, Parkinson's disease and stroke. This increase in TSPO expression has been reported to coincide with the process of microglial activation, whereby the brain's intrinsic immune system becomes active. Therefore, by using recently developed high affinity, selective TSPO ligands in conjunction with functional imaging modalities such as positron emission tomography (PET), it becomes possible to study the process of microglial activation in the living brain. A number of high affinity ligands, the majority of which are C,N-substituted acetamide derivatives, have been successfully radiolabelled and used in in vivo studies of the TSPO and the process of microglial activation. This review highlights recent achievements (up to December 2008) in the field of functional imaging of the TSPO as well as the radiosyntheses involved in such studies.