Over the past ten years, a variety of imaging techniques have been developed that allow non-invasive detection of gene expression within the brain of intact mammals, ranging from mouse to man. The basic concepts of these imaging techniques, including positron emission tomography, single photon emission computed tomography, magnetic resonance imaging and spectroscopy, bioluminescence imaging and fluorescent imaging, are discussed. The expression of imaging reporter genes can be detected and quantified by these imaging techniques, which allow to unravel the temporospatial dynamics of gene expression within the intact living animal. Different imaging reporter genes have been developed each with their specific use in the basic and clinical neurosciences. Applications of reporter gene imaging can be found in neurooncology, infectious disease of the central nervous system, brain gene transfer, neural cellular therapy and in transgenic mice. Strategies that aim to image gene expression based on detection of mRNA levels have also been developed. We anticipate that these techniques will have a strong impact on preclinical neuroscience and will be of utmost importance in the implementation of gene and cell therapy for diseases of the brain.