The rostromedial medulla, including the nucleus gigantocellularis (NGC) and magnocellularis (NMC), plays a role as a relay nucleus for both the sensory and motor systems. The NGC / NMC is important in the modulation of somatic and visceral activities. Electrophysiological and pharmacological studies have shown that the NGC / NMC is involved in nociception, locomotion, regulation of basal muscle tone, sleep, as well as cardiovascular and pulmonary activities. Pharmacological and electrical stimulation of the NGC / NMC can produce opposite effects on physiological functions: analgesia or hyperalgesia, and suppression or facilitation of motor activity, depending on the subgroups of neurons activated and the states of the sleep-wake cycle at the time of stimulation. Sensory inputs including noxious and innocuous stimuli converge on the NGC / NMC. The NGC / NMC also plays a role as a relay nucleus, which sends sensory information to the higher centers. The NGC / NMC receives projections from the supra-bulbar motor facilitatory and inhibitory areas, and plays an important role in the regulation of motor activity. Pharmacologically, neurons in the NGC / NMC contribute to opioid, glutamate, GABA, acetylcholine, dopamine, substance P, neurotensin, hypocretin (orexin), and cannabinoid mediated sensory and motor activities, as well as cardiovascular and pulmonary functions. In this review, we will discuss the neuronal morphology, physiological functions and pharmacological characterization of the rostromedial medulla. We will consider the evidence that dysfunction of the NGC / NMC is a factor in a number of neurological diseases, including Parkinsons disease, restless legs syndrome, periodic leg movement, REM sleep behavior disorder, amyotrophic lateral sclerosis and narcolepsy.