Computed tomographic colonography (CTC), also known as virtual colonoscopy, is an emerging alternative technique for screening of colon cancers. CTC uses CT to provide a series of cross-sectional images of the colon for detection of polyps and masses. Fecal tagging is a means of labeling of residual feces by an oral contrast agent for improving the accuracy in the detection of polyps. Computer-aided diagnosis (CAD) for CTC automatically determines the locations of suspicious polyps and masses in CTC and presents them to radiologists, typically as a second opinion. Despite its relatively short history, CAD has become one of the mainstream techniques that could make CTC prime time for screening of colorectal cancer. Rapid technical developments have advanced CAD substantially during the last several years, and a fundamental scheme for the detection of polyps has been established, in which sophisticated 3D image processing, analysis, and display techniques play a pivotal role. The latest CAD systems indicate a clinically acceptable high sensitivity and a low false-positive rate, and observer studies have demonstrated the benefits of these systems in improving radiologists' detection performance. Some technical and clinical challenges, however, remain unresolved before CAD can become a truly useful tool for clinical practice. Also, new challenges are facing CAD as the methods for bowel preparation and image acquisition, such as tagging of fecal residue with oral contrast agents, and interpretation of CTC images evolve. This article reviews the current status and future challenges in CAD for CTC without and with fecal tagging.