In this second article, we review the various strategies and applications that make use of reporter genes for molecular imaging of the brain in living subjects. These approaches are emerging as valuable tools for monitoring gene expression in diverse applications in laboratory animals, including the study of gene-targeted and trafficking cells, gene therapies, transgenic animals, and more complex molecular interactions within the central nervous system. Further development of more sensitive and selective reporters, combined with improvements in detection technology, will consolidate the position of in vivo reporter gene imaging as a versatile technique for greater understanding of intracellular biologic processes and underlying molecular neuropathology and will potentially establish a future role in the clinical management of patients with neurologic diseases.