Gastrointestinal (GI) and hepatic conditions are a leading source of health-care utilization today. A significant segment of the over-the-counter and prescription drug market comprises drugs used to alleviate symptoms localized to the alimentary tract. The discovery of new mechanisms of disease pathogenesis will inform the future development of targeted therapeutics for conditions managed by gastroenterologists and hepatologists. Newly approved drugs and evolving mechanistic targets offer a promising trajectory to both clinicians and patients with GI and liver disorders.