Numerous classes of drugs could benefit by improved delivery using a gastroretentive delivery system, including drugs with a short half-life, a selective absorption window, those for local delivery to the gastromtestinal tract, and formulations for which improved pharmacokinetic control are required (1-5). An ideal gastroretentive drug delivery system should be small enough to swallow, to not swell or expand in the esophagus and/or intestines, display controlled-release properties, be sufficiently rigid to remain intact in the stomach, decrease in size or degrade after it has performed its function, while at the same time showing minimal food effects following administration (3). Gastrointestinal retention system (GIRESTM, Merrion Pharmaceuticals, PLC, Dublin, Ireland) is a platform technology that addresses these challenges. This chapter briefly describes some in vitro and in vivo human studies that demonstrate the safety and effectiveness of GIRESTM.