- The gastrointestinal tract (GIT) is a long and complex organ, with significantly variable characteristics throughout. It is broadly divided to several segments: the stomach; the small intestine which is subdivided to duodenum, jejunum, and ileum; and the colon. Each segment has its own unique environment. Conditions in each segment are dependent on a multitude of factors. The focus of this chapter is gastroretentive dosage form (GRDF). This term encompasses several technologies with one common feature: they are designed to resist the normal tendency of the stomach to clear its content, resulting in a targeted and controlled release of the active moiety to the upper GI tract. A special emphasis is given for the rationale for GRDF, different GRDF technologies, and their unique application. In conclusion, segment-specific targeting technologies are a highly important research field; a thorough understanding of the determinants of gastrointestinal environment, considering the whole of the human intestine, is crucial for successful targeting of drugs to specific gastrointestinal regions and exploitation of the variable intestinal conditions for better drug delivery and therapeutic effect.