The cell is the basic unit of life. The attainment of a nucleus to house the genetic material is thought to have provided a distinct advantage to the evolving cell, ultimately allowing the emergence of differentiated, specialized cells. Hoarding evidence suggests that genomes are organized non-randomly into complex 3D configurations that vary according to cell type, stage of development, differentiation and disease status. The principles, which guide higher order organization, the mechanisms responsible for establishment, maintenance and alterations of higher order genome, and the functional consequences of aberrant genome and nuclear organization, have become zones of intense interest.