The ability to predict transporter effects on drug absorption and disposition involves concurrent consideration of many chemical and physiological variables and the effect of food on the rate and extent of availability adds further complexity due to postprandial changes in the gastrointestinal (GI) tract. A system that allows for the assessment of the multivariate intestinal interplay occurring following administration of an oral dose, in the presence or absence of a meal, would greatly benefit the early stages of drug development. In this thesis research, we focus on how the Biopharmaceutics Classification System (BCS) and our laboratory’s Biopharmaceutics Drug Disposition Classification System (BDDCS) in combination with in vitro and in vivo model systems are useful in predicting when intestinal transporter function may be clinically relevant. We investigate the role of transporters in food-drug interactions specifically asking the question: Could high fat meals be inhibiting transporters? We find that simulated physiological intestinal media, designed for dissolution testing, does not allow for transporter effects to be isolated from viscosity and solubility effects. However, a less complex media supplemented with monoglycerides to mimic the postprandial intestine is applicable to bidirectional transport studies resulting in inhibition of efflux but not uptake. We find that the Caco-2 cell system is representative of the human intestine and is an adequate model for studies with Class 1 and 2 compounds but an inadequate model for Class 3 and 4 compounds. Our data suggest that intestinal transporters belong on the list of variables that must be considered in food-drug interactions. Overall, the results from this thesis research reinforce the importance of intestinal transporters in drug absorption and demonstrate how in vitro model systems, when properly applied, can be a powerful and valuable predictive tool in determining clinical relevance.