Drug absorption from the gastrointestinal (GI) tract and the impact of GI surgery and disease on drug absorption are discussed. Recommendations are made to manage problems of drug malabsorption. Absorption from the GI tract is a first-order process described by its rate and extent. GI surgery changes the anatomy of the GI tract and alters important variables in the absorption process. In the wake of procedures which diminish small bowel surface area, the extent of absorption of phenytoin, digoxin, cyclosporin, aciclovir, hydrochlorothiazide and certain oral contraceptives is reported to be reduced. The underlying cause of the reduction is unknown. When gastric emptying time or pH are altered by surgery, the rate of drug absorption appears to be reduced. However, it is not clear which variable is more important in determining therapeutic effects. The effects of coeliac and inflammatory bowel diseases on the distribution and clearance of drugs must be considered before attributing abnormal serum concentrations of drugs to malabsorption. GI disease may slow gastric emptying and delay the complete absorption of drugs when their rate of absorption depends on gastric emptying time. Other inflammatory GI diseases such as graft-versus-host disease (GVHD) of the gut, Behçet's syndrome and scleroderma involving the GI tract may directly reduce absorption of drugs such as cyclosporin, amitriptyline, benzodiazepines, anticonvulsants, paracetamol (acetaminophen) and penicillamine. GI diseases which alter gut pH affect the absorption only of drugs with limited water solubility and pH-dependent dissolution such as ketoconazole. Clinicians should be aware of the variable absorption seen after GI disease and surgery and monitor their patients accordingly.