The cardiac neuraxis is integral to cardiac physiology, and its dysregulation is implicated in cardiovascular disease. Neuromodulatory therapies are being developed that target the cardiac autonomic nervous system (ANS) to treat cardiac pathophysiology. An appreciation of the cardiac neuroanatomy is a prerequisite for development of such targeted therapies. Here, we provide a review of the current understanding of the cardiac ANS. The parasympathetic and sympathetic nervous systems are composed of higher order cortical centers, brainstem, spinal cord, intrathoracic extracardiac ganglia and intrinsic cardiac ganglia. A series of interacting feedback loops mediates reflex pathways to exert control over the cardiac conduction system and contractile tissue. Further exploration of this complex regulatory system promises to yield neuroscience-based therapeutics for cardiac disease.