OBJECTIVES: Colorectal cancer (CRC) is largely preventable using screening to detect and remove adenomatous polyps during flexible sigmoidoscopy (FS) and colonoscopy, or to identify early-stage cancers with fecal occult blood testing (FOBT) and fecal immunochemical testing (FIT). Despite the proven efficacy of CRC screening (CRCS), screening rates remain relatively low. Patient’s psychological barriers seem to affect participation in CRCS. We conducted a comprehensive review of the literature to identify psychological barriers associated with CRCS. METHODS: We conducted a systematic review of studies reporting on psychological factors and colorectal cancer screening from 2004 to 2014 using MEDLINE/PubMed and Google Scholar.  Limiting  the search to the English language reports, the search strategy involved combining (a) colorectal cancer screening-related key words (eg, ‘‘cancer,’’ ‘‘screening,’’ ‘‘adherence,’’ ‘‘colonoscopy,’’ ‘‘sigmoidoscopy,’’ ‘‘chemotherapy’’) and (b) words pertaining to or synonymous with fear (eg, ‘‘fear,’’ ‘‘anxiety,’’ ‘‘embarrassment,’’ ‘‘belief). RESULTS: Of the 17 articles identified, 11 explored general barriers among the U.S. population, while the other 6 examined specific barriers such as fear, disgust, perceptions, attitudes, knowledge, and medical mistrust. Six of the studies were qualitative studies, 4 were quantitative study, 3 used a mixed methods approach and 4 were reviews. Sample sizes varied from 23-55 subjects in the qualitative studies; and 151-454 subjects in the quantitative studies. Common perceived barriers included mistrust of the healthcare system, embarrassment of being undressed in front of a provider, the nature of the screening exam itself, fear of being a burden to the family, and fatalism. CONCLUSIONS: The results of this study demonstrate that psychological factors such as fear of the test itself, of cancer diagnosis, of burdening family members, and embarrassment play a role in determining whether patients would opt for CRCS. In order to improve the quality of care and successfully increase screening rates for CRC, overcoming these barriers is of utmost importance.