Infantile hypertrophic pyloric stenosis (IHPS) is the most common surgical cause of vomiting in infants. Despite numerous hypotheses, the aetiopathogenesis of IHPS is not fully understood. Genetic, extrinsic and hormonal factors have been implicated in the pathogenesis of the disease. Furthermore, abnormalities of various components of the pyloric muscle such as smooth muscle cells, growth factors, extracellular matrix elements, nerve and ganglion cells, synapses, nerve supporting cells, neurotransmitters and interstitial cells of Cajal have been reported. Recently, genetic studies have identified susceptibility loci for IHPS and molecular studies have concluded that smooth muscle cells are not properly innervated in IHPS.