The development of effective medical control of acid hypersecretion in ZES patients, precluding the need for total gastrectomy, became possible with the development of first, histamine H2 receptor antagonists [52,98,150], and later by the late 1980s, the PPIs [32,33,34], which are now the drugs of choice in these patients because of their long duration of action, lack of tolerance, and continued efficacy when used once or twice a day [22,28]. The gene discussed is HRH2; the disease is Zollinger-Ellison syndrome.