Proton pump inhibitors (PPI) are now one of the most widely used classes of drugs. PPIs have proven to have a very favorable safety profile and it is unusual for a patient to stop these drugs because of side effects. However, increasing numbers of patients are chronically taking PPIs for gastro esophageal reflux disease and a number of other common persistent conditions, therefore the long-term potential adverse effects are receiving increasing attention. Nowadays as PPI are the main drugs used for peptic ulcer disease and GERD ,a part from this they are also preferred in drug induced gastric irritation .In this article these studies are systematically examined, as well as the studies of the effects of chronic PPI usage on VB12 calcium , absorption which leads to neurologic disorders and osteoporosis. In general the studies in each of three areas have led to differing conclusions, but when examined systematically, a number of the studies are showing consistent results that support the conclusion that long-term adverse effects on these processes can have important clinical implications.