The nuclear lamina is a filamentous nuclear structure intimately connected to the inner nuclear membrane. It is composed of lamins, which are also present in the nuclear interior, and lamin-associated proteins. The nuclear lamina is involved directly or indirectly in many nuclear activities, including DNA replication and transcription, nuclear and chromatin organization, cell cycle regulation, cell development and differentiation, nuclear migration and apoptosis. Mutations in nuclear lamina genes cause a wide range of heritable human diseases, the molecular mechanisms for which are not well understood. This review describes our current knowledge of interactions between nuclear lamina proteins and chromatin, chromatin-remodeling factors, specific transcription factors and RNA polymerase II transcription machinery. Recent studies provide new insights into the nature and regulation of these interactions and suggest additional roles for the nuclear lamina.