In peripheral tissues, dopamine is released from neuronal cells and is synthesized within specific parenchyma. Dopamine released from sympathetic nerves predominantly contributes to plasma dopamine levels. Despite growing evidence for peripheral source and action of dopamine and the widespread expression of dopamine receptors in peripheral tissues, most studies have focused on functions of dopamine in the central nervous system. Symptoms of several brain disorders, including schizophrenia, Parkinson's disease, attention-deficit hyperactivity disorder, and depression, are alleviated by pharmacological modulation of dopamine transmission. Regarding systemic disorders, the role of dopamine is still poorly understood. Here we describe the pioneering and recent evidence for functional roles of peripheral dopamine. Peripheral and central dopamine systems are sensitive to environmental stress, such as a high-fat diet, suggesting a basis of covariance of peripheral and central actions of dopaminergic agents. Given the extended use of such medications, it is crucial to better understand the integrated effects of dopamine in the whole organism. Delineation of peripheral and central dopaminergic mechanisms would facilitate targeted and safer use of drugs modulating dopamine action. We discuss the increasing evidence for a link between peripheral dopamine and obesity. This review also describes the recently uncovered protective actions of dopamine on energy metabolism and proliferation in tumoral cells.