Proton pump inhibitors (PPIs) are a group of gastric acid suppressing drugs, that are strong and long-lasting inhibitors of the proton pump (referred to as acid pump antagonists). They work by irreversibly blocking the H+/K+ ATPase. PPIs are used to treat peptic ulcer disease, gastroesophageal reflux disease, nonsteroidal anti-inflammatory drug-induced gastrointestinal lesions, and Zollinger-Ellison syndrome. The structure of PPIs are similar, they all have a similar core with a sulphur atom chiral center combined with different substituent groups. In relation to the sulphur atom chiral center, the pharmacodynamics, pharmacokinetics are diverse between the racemates and their stereoisomers, which are mainly observed in the following aspects. In regards to pharmacodynamics, the main features of the similarities and differences involve the duration of drug action and the ability to control nocturnal gastric acid secretion. In regards to pharmacokinetic and metabolic pathways, the similarities and differences are measured by the pharmacokinetic and metabolic parameters. These parameters including time to maximal plasma concentration (Tmax), maximal plasma concentration (Cmax), area under the plasma concentration curve (AUC), bioavailability (F) and elimination half-life (t1/2). Compare to the racemates, the stereoisomer (the R-one or the S-one) exhibited less individual differences and better efficiency in acid secretion control. Nowadays, the main reason for PPI development is not so much in relation to the therapeutic effects of these drugs, but is more in the realm of providing longer duration, faster time of onset and better nocturnal gastric acid secretion control. Structure improvement and development of stereoisomer drugs are the two directions for the new generation PPIs. Esomeprazole, dexlansoprazole, ilaprazole and revaprazan, have recently been developed on these principles. However, due to debates on the necessity and superiority of these new drugs, more validation studies are needed.