Within the last decades, functional magnetic resonance imaging (fMRI) has widely replaced previously used methods such as positron emission tomography (PET) or single photon emission computed tomography (SPECT) in the assessment of functional brain activation. However, PET and SPECT remain important tools for in vivo assessment of neurotransmitter receptors and transporters and for the assessment of baseline regional cerebral blood flow. PET and SPECT also provide a unique opportunity to directly quantify genotype effects on protein expression. We review current nuclear imaging techniques for quantification of genotype effects on neurotransmitter receptors and transporters. Furthermore, we describe first multimodal imaging studies that combined PET, fMRI and genetic data in order to measure effects of genotype or the availability of receptor or transporters on functional brain activation. The clinical relevance of these studies will be illustrated and discussed.