Visceral hypersensitivity is now recognised as a major pathophysiological mechanism in functional gastrointestinal disorders of the upper gastrointestinal tract. In patients with non-cardiac chest pain and functional dyspepsia, a high prevalence of visceral hypersensitivity has been indeed observed. In these patients, luminal physiological stimuli can be perceived as unpleasant or even painful. Although the fine mechanisms underlying such "aberrant perceptions" are yet not fully clarified, it is thought that an altered activation of the gut-wall receptors, an altered conduction of sensory inputs at the level of neural pathways, or an impaired processing of the sensations at the level of brain, may occur along the brain-gut axis. So far, drugs able to reduce hypersensitivity, that target each of the constituents of the stimuli-perception chain, have the therapeutic potential to reduce visceral hypersensitivity and, thus, to improve the symptoms. In this context, the availability of new agonists/antagonists to neurotransmitters offers a new exciting tool for the treatment of functional disorders of the upper gastrointestinal tract.