Traditional methods for colorectal cancer (CRC) screening have reduced rates of malignancy and death; however, low compliance and morbidities associated with invasive techniques have encouraged efforts for establishing equally effective, less invasive novel screening approaches. We review the current state of novel screening approaches in CRC to include CT colonography, fecal DNA, DNA methylation, micro-RNA, and protein and molecular markers. J. Surg. Oncol. 2012; 105:459–467. © 2012 Wiley Periodicals, Inc.