In gastroenterology, as in other medical specialties, new potential therapies, both pharmaceutical and invasive, continually appear on the horizon, always with great initial enthusiasm. Over time, these will either prove to be failures or will find their appropriate level of use in our therapeutic armamentarium. When faced with promising new therapies, we should always wonder whether they are effective and safe and whether they are really better than the current ones. One is therefore justified to attempt from time to time a critical review of the recent developments in the field in order to provide a glimpse of what may lie ahead. The pharmacotherapy of the gastrointestinal (GI) tract, with its large mucosal area (over 400 m2, more than 200-fold greater than the area of the skin), remains a unique challenge. In many ways, the intestinal milieu represents a microcosm of the entire body. It possesses indeed its own intrinsic nervous and endocrine systems, its barrier both to the external and internal environments of the body, and its own intrinsic mucosal immune system, namely the so-called gut-associated lymphoid tissue (GALT). Each of these enteric systems can account for pathophysiology and can contribute to the clinical picture of the digestive disorders. Thus, therapeutic intervention for diseases of the GI tract is particularly demanding and must be strategically targeted, with the potential for drug side effects representing a considerable liability. And indeed, gastroenterology is characterized by an overwhelming load of unmet needs. In this issue, devoted to Advances in GI Pharmacology and Therapeutics, world-renowned experts in major areas of digestive pathology discuss in detail those classes of drugs which hold the greatest promise of addressing unmet clinical needs and whose members have already reached clinical testing. Topics that are covered in extenso include: acid suppressant therapy, anti-diarrheal agents, serotoninergic drugs, CCK-antagonists, neurokinin receptor-antagonists, peripheral opioid receptor ligands, drugs affecting visceral sensitivity, rescue anti-H. pylori treatments, biologic therapies in IBD, probiotics, pharmacologic treatment of acute pancreatitis, and emerging therapies for viral hepatitis and liver fibrosis. This issue, which includes much of the information difficult to collect from other scattered sources, will be a valuable text for pharmacologists, gastroenterologists and all doctors engaged in the everyday management of GI and liver diseases.