The diacylglycerol-kinases are a family of related lipid kinases. There are currently 10 known isoforms of diacylglycerol kinases that are categorized into five groups based on similarities in their primary sequence. All of these enzymes catalyze the transfer of the γ-phosphate of ATP to one lipid second messenger, diacylglycerol, thereby generating another lipid second messenger, phosphatidic acid. As a result, they are uniquely poised to regulate the relative levels of these two key second messengers. These enzymes show considerable diversity in their cellular and sub-cellular distribution which suggests a great diversity in physiological functions. One sub-cellular compartment that is receiving a considerable attention is the nucleus. A number of DGKs have been found to reside in, or translocate to the nucleus in response to agonists. In this review we focus primarily on the nuclear localization, modulation of intrinsic enzymatic activity, and the potential physiological roles of the six diacylglycerol kinases that have been found in the nucleus: DGK-alpha, DGK-gamma, DGK-delta, DGK-zeta, DGK-iota, and DGK-theta.