Genomes are defined by their primary sequence. The functional properties of genomes, however, are determined by far more complex mechanisms and depend on multiple layers of regulatory control processes. A key emerging contributor to genome function is the architectural organization of the cell nucleus. The spatial and temporal behavior of genomes and their regulatory proteins are now being recognized as important, yet still poorly understood, control mechanisms in genome function. Combined cell biological, molecular and computational analysis of architectural aspects of genome function has added a further dimension to the investigation of some of the most fundamental cellular processes including transcription and maintenance of genome integrity. The complete elucidation of the contribution that nuclear architecture makes to gene expression will be required to fully understand physiological processes such as differentiation, development and disease at the cellular level. Here I give an overview of some of the emerging concepts in the study of in vivo genome organization and function.