BACKGROUND There are many factors that can affect the absorption process of orally administered drugs. Intestinal transporters play an important role in drug absorption. These transporters are divided into two major classes: the solute carriers and the ATP-binding cassette (ABC) transporters. P-glycoprotein (P-gp), belonging to the ABC transporter superfamily, flushes out the substrate drugs from a cell, thus regulating the intestinal absorption of drugs. METHODS This review gives a brief overview of uptake and efflux transporters localized in the intestine. However, because P-gp has been identified as an important underlying mechanism of drug interactions in humans, the review is strongly focused on summarizing the currently available data on the impact of P-gp for absorption of drugs. CONCLUSIONS The concomitant use of P-gp substrates and inhibitors (preferably in a single nanocarrier formulation) could be an effective and safe way to improve the bioavailability of drugs. It seems the study of P-gp and modulating its activity may be an interesting therapeutic goal to be considered in future research.