AIM: To review and summarize drug metabolism and its related interactions in prescribing drugs within the similar therapeutic or structural class for gastrointestinal disease treatment so as to promote rational use of medicines in clinical practice.METHODS: Relevant literature was identified by performing MEDLINE/Pubmed searches covering the period from 1988 to 2006. RESULTS: Seven classes of drugs were chosen, including gastric proton pump inhibitors, histamine H2-receptor antagonists, benzamide-type gastroprokinetic agents, selective 5-HT3 receptor antagonists, fluoroquinolones, macrolide antibiotics and azole antifungals. They showed significant differences in metabolic profile (I.e., the fraction of drug metabolized by cytochrome P450 (CYP), CYP reaction phenotype, impact of CYP genotype on interindividual pharmacokinetics variability and CYP-mediated drug-drug interaction potential). Many events of severe adverse drug reactions and treatment failures were closely related to the ignorance of the above issues. CONCLUSION: Clinicians should acquaint themselves with what kind of drug has less interpatient variability in clearance and whether to perform CYP genotyping prior to initiation of therapy. The relevant CYP knowledge helps clinicians to enhance the management of patients with gastrointestinal disease who may require treatment with polytherapeutic regimens.