It is with great excitement that we introduce this special issue of Gastroenterology on colorectal cancer. It is hard to believe that it has been 8 years since the last special issue devoted to this important topic, and the reviews and commentaries featured will speak both to the progress as well as the continued challenges we face. The importance of colorectal cancer is highlighted by the fact that colorectal cancer remains the third most common cancer and the second leading cause of cancer deaths in both men and women.