Recent studies of the nuclear envelope (NE) have emphasized its role in linking the nuclear and cytoplasmic compartments of mammalian cells. The inner face of the NE is bound to chromatin and this interaction is involved in regulating DNA replication and transcription. The outer face of the NE binds to different components of the cytoskeleton, and these interactions are involved in nuclear positioning. Many disease causing mutations in genes encoding NE proteins cause significant changes in nuclear architecture and cytoskeletal interactions with the NE. These mutations are also providing important new insights into nuclear-cytoplasmic interactions.