Absorption windows in the proximal gut can limit the bioavailability of orally administered compounds and can be a major obstacle to the development of controlled release formulations for important drugs. Methods to increase the residence of drug formulations at or above the absorption window are discussed in this review. Two main approaches are presently being explored: (i) bioadhesive microspheres that have a slow intestinal transit; and (ii) the gastroretentive dosage system, which is based on multiparticulates or large single unit systems. A good understanding of gastrointestinal transit in humans and the effect of factors such as food can be helpful in the design of rational systems that will have clinical benefit.