Colorectal cancer afflicts approximately 150,000 Americans annually, approximately one third of whom die [1]. It afflicts approximately 250,000 annually in Europe [2] and approximately I million people worldwide [3]. A review of the pathophysiology, clinical presentation, and diagnosis of colon cancer is important and timely. This field is changing rapidly because of breakthroughs in the molecular basis of carcinogenesis and in the technology for colon cancer detection and therapy. This article provides an overview of the pathophysiology, clinical presentation, and management of colon cancer, with a focus on recent advances, to help clinicians and gastroenterologists appropriately screen, diagnose, and manage patients to reduce mortality from this cancer. The other articles in this issue focus on individual aspects of colon cancer in detail.