The model systems that are currently used to determine the intestinal permeability characteristics of discovery compounds often represent a combination of high-throughout, but less predictive, in silico and in vitro models and low-throughput, but more predictive, in vivo models. Cell-based permeability models have been integrated into the discovery paradigm for some time and represent the "method of choice" across the industry. Here, in addition to an objective analysis of the utility of cell culture models for permeability screening, anticipated future trends in the field of cell culture models are discussed.