The oral route of drug administration remains the most popular and convenient route of administration, despite its many shortcomings and challenges. Although the advantages associated with this route far outweigh any limitations, a prominent limitation relates to the interactions of drugs with intestinal membrane transporters. The complexities of these interactions and their impact on drug absorption and absorption variability are only now becoming recognized. The rapidly growing awareness of transporter-mediated secretion, saturable absorption, and even the concerted actions of transporters in intestinal drug absorption and secretion has attracted the attention of pharmaceutical scientists in academia, the pharmaceutical industry and the regulatory agencies. This is evidenced by the recent rapid accumulation of data in the literature, the routine conducting of transport studies in the discovery and development of drugs, and finally by the recognition of the importance of transporter (e.g. P-glycoprotein and OATP) mediated secretion of drugs by regulatory authorities such as the U.S. Food and Drug Administration. In this mini-review, we focus on the handful of absorptive and secretory transporters that have been relatively well studied and illustrate the impact of these intestinal transporters on oral drug absorption using published reports from preclinical and clinical studies.