Bariatric surgery constitutes an approach to the management of obesity in which the anatomy of the gastrointestinal tract is altered to reduce access of nutrients to absorptive surfaces, to restrict the absolute volume of material that can be ingested at once, or a combination of the two. Roux-en-Y gastric bypass (RYGB), currently the most common bariatric surgical procedure worldwide, has both malabsorptive and restrictive features. RYGB can be associated with alterations in absorption and disposition of medications. However documenting and predicting the specific pharmacokinetic changes associated with RYGB is a difficult research challenge. Because obesity and weight loss themselves can alter drug disposition, it may be difficult or impossible to resolve whether pharmacokinetic alterations in post-RYGB patients are due to the surgery itself as opposed to the subsequent weight loss. Changes in disposition of medications may be drug-specific as opposed to generalized. Further, statistically significant modifications in drug disposition are not necessarily of clinical importance. Clinical decisions on medication use in post-bariatric surgical patients should be based on a review of the original literature dealing with the particular drug in question.