The ureter is possibly the least studied and most poorly understood organ of the urinary tract. The pathophysiologic basis underlying the use of α-blockers to improve ureteral stone passage or to treat ureteral stent symptoms is poorly understood. This, in part, may explain why clinical studies of medical expulsive therapy for ureteral stone passage are fraught with conflicting data. Methods to study human ureter in vivo are few and challenging. The findings of many of the ureteral studies are from observational in vitro studies and were evaluated in other animal species that may not be applicable in human beings. There are few mechanistic studies evaluating the underlying molecular pathophysiologic mechanisms of human ureter. This is critical to our understanding and treatment of stent symptoms, including the development of a patient friendly ureteral stent and for the pharmacologic modulation of ureteral activity. The following is an overview of some of the observational and mechanistic ureteral studies evaluating the pharmacologic and stent effects, including potential areas for further research.