Targeting drugs to the gastrointestinal tract has been and continues to be an active area of research. Gut-targeting is an effective means of increasing the local concentration of active substance at the desired site of action while minimizing concentrations elsewhere in the body that could lead to unwanted side-effects. Several approaches to intestinal targeting exist. Physicochemical property manipulation can drive molecules to large, polar, low absorption space or alternatively to lipophilic, high clearance space in order to minimize systemic exposure. Design of compounds that are substrates for transporters within the gastrointestinal tract, either uptake or efflux, or at the hepato-biliary interface, may help to increase intestinal concentration. Prodrug strategies have been shown to be effective particularly for colon targeting, and several different technology formulation approaches are currently being researched. This review provides examples of various approaches to intestinal targeting, and discusses challenges and areas in need of future scientific advances.