Carcinoma of the gastrointestinal tract is the most common internal malignancy affecting men and women in Western countries. Chronic intestinal inflammation, especially of the colon, is also a Western disease and correlates with a significantly increased risk of developing cancer. This has suggested that the immune processes involved in both conditions might share some common pathways. Indeed, there is increasing evidence that phosphatidylinositol 3-kinases (PI 3-kinases) are involved in both the pathogenesis of colorectal carcinoma and intestinal inflammation. Here, we discuss this rapidly progressing area of research, presenting evidence for a pivotal role of PI 3-kinase(s) in intestinal pathophysiology.