Neuronal nicotinic acetylcholine receptors (nAChRs), ubiquitously distributed in the human brain, are implicated in various neurophysiological processes and in the pathophysiology and/or treatment strategies of Alzheimer's and Parkinson's diseases, Tourette's syndrome, epilepsy, schizophrenia, depression, and anxiety, as well as being particularly affected in tobacco dependence/withdrawal. In the past two decades, researchers have developed an extensive series of radioligands for the assessment of nAChRs in vivo through emission tomography, PET and SPECT. Several radioligands, derivatives of A-85380: 2-[(18)F]FA, 6-[(18)F]FA and 5-[(123)I]IA, are now being employed for the evaluation of nAChR in humans with PET and SPECT. Displaying better imaging properties than (11)C-nicotine and a better toxicity profile than epibatidine analogs, they have allowed quantification of thalamic nAChR in the human brain. Nevertheless, A-85380 derivatives still exhibit slow brain kinetics and a moderate signal-to-noise ratio. Current research efforts on the part of PET/SPECT radiochemists, therefore, have focused on development of new, highly specific and highly selective nAChR radioligands with improved brain kinetics that are able to localize high-affinity nAChRs in vivo. Key examples of new PET/SPECT ligands that are derived from several different structural classes are discussed along with a review of their chemical as well as their in vitro and/or in vivo properties. In particular, new PET nAChR radioligands will be examined that either present faster brain kinetics allowing simple and reliable quantification approaches or higher binding potentials suitable for the evaluation of extrathalamic nAChR.