Cell communication, an essential component of integrated physiological function in multicellular organisms, is mediated largely through informational molecules, such as hormones and neurotransmitters. After binding to specific receptors, these first messengers activate intracellular signaling cascades and, thereby, translate extracellular messenger levels into intracellular events. Atrial fibrillation is associated with significant electrophysiological and structural alterations of atrial tissue. Most of these changes seem to be related to activation of signal transduction systems at the molecular atrial level. This review will describe the role and regulation of different signal transduction systems in fibrillating atria.