Irritable bowel syndrome (IBS) is a common condition with a complex and largely unknown etiology. There is no cure, and treatment options are mainly directed to the amelioration of symptoms. IBS causes reduced quality of life and poses considerable repercussions on health and socioeconomic systems. There is a heritable component in IBS, and genetic research is a valuable tool for the identification of causative pathways, which will provide important insight into the pathophysiology. However, although some gene-hunting efforts have been conducted and a few risk genes proposed, IBS genetic research is lagging behind compared to other complex diseases. In this mini-review, we briefly summarize existing genetic studies, discuss the main challenges in IBS genetic research, and propose strategies to overcome these challenges for IBS gene discovery.