The oral delivery of drugs is considered by decision-makers in the pharmaceutical industry to be the most appealing route of administration. This belief has led to the identification of many very successful drugs, but also to the downfall of some promising therapeutics that failed to meet criteria required for sufficient oral bioavailability. Efforts to correct these deficiencies have led to a plethora of creative strategies to overcome the physical, chemical, and biological barriers that limit the efficient and consistent delivery of drugs that are not readily absorbed following oral administration. The goal of this perspective is to describe these barriers to oral drug delivery in relation to some of the work currently being undertaken by the community of European scientists. This perspective is not intended to be inclusive and the author apologizes in advance to the many scientists working in Europe whose recent work was not included.