Advances have been made in several areas of second messenger and signal transduction research in mood disorders.Evidence from postmortem brain and clinical studies which implicates disturbances in signal-transducing guanine nucleotide binding proteins in bipolar disorder is discussed as well as results of studies suggesting that mood stabilizing agents, particularly lithium, act on intracellular signaling targets. Findings supporting disturbances in inositol phospholipid and intracellular calcium signaling systems in affective disorders are also described.