Oral administration is the most common route for drug administration. However, after oral administration, the absorption may be erratic and incomplete. P-glycoprotein, an efflux transporter localized in the enterocyte, limits the absorption of transported drugs extruding them back to the intestinal tract. The interaction between new drug candidates and P-glycoprotein is investigated in vitro during early stages of drug development. However, it is uncertain how well the in vitro studies actually predict the in vivo P-glycoprotein effect on the extent of oral absorption, since the in vitro and in vivo correlation has not been achieved. In the present review, the recent approaches to compare the in vitro and in vivo data are described and parameters are proposed that could be adequate for a reliable in vitro and in vivo correlation of P-glycoprotein contribution on intestinal absorption. The present article identifies an evident lack of suitable in vivo data. A significant in vitro and in vivo correlation would increase the value of in vitro studies and could reduce costs during the process of drug development.