The nuclear periphery has conventionally been considered as a zone of inactive chromatin and transcriptional repression. Recent studies have shed new light on the types of sequences associated with proteins of the nuclear periphery in mammalian cells and have investigated the functional significance of artificially locating genes there. The results of these studies reveal a complex picture. Whilst the edge of the nucleus does seem to have a direct effect on the expression of some genes, other genes seem unaffected by their proximity to the nuclear periphery. Moreover, the nuclear periphery itself is heterogeneous, with microdomains of differing compositions, associating with different genomic regions and probably having differential effects on genome function.