Background: Colorectal cancer has emerged as the most common cancer in Singapore. The quality of life has become increasing important in measuring the outcomes of colorectal cancer patients and the impact of the disease on a person's life. The objective of this review was to synthesize the best available evidence on the factors that have an impact on the Quality of Life of patients with colorectal cancer. All primary quantitative studies published in English were considered for inclusion in the review. An extensive electronic database search was conducted since database inception to the December 2010 to identify potential relevant studies using CINAHL, PUBMED/MEDLINE, PsycINFO (OVID, Scopus, ScienceDirect, Springerlink, Web of Science (Social Science Citation Index), Expanded Academic ASAP, Mosby's Nursing Consult, Sociological Abstracts, Mednar and Proquest. Two independent reviewers assessed the eligibility and methodological quality of the papers selected prior to inclusion using the appropriate standardised critical appraisal checklists from the Joanna Briggs Institute Meta Analysis of Statistics Assessment and Review Instrument. The two reviewers resolved disagreement by discussion. Quantitative data were extracted from relevant studies using the appropriate standardised data extraction tool. Twenty papers were selected and assessed for relevancy. After further review, fifteen papers that met the level of methodological standard were included in this review. The extracted data included specific details about the interventions, participants' demographics, study methods and any outcomes of significance to the aim of the review. A meta-analysis was not appropriate due to the heterogeneity of methodology in the included studies, thus the findings were presented in a narrative form. The review included fifteen studies which consisted of twelve descriptive studies and the other three were case-control studies. The findings indicated that patients with colorectal cancer continue to suffer from depression, distress and bowel related problems such as constipation and diarrhoea which impacted their quality of life. European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire, Core Module (QLQ-C30), European Organisation for Research and Treatment of Cancer (EORTC) Colorectal Cancer-Specific Quality of Life Questionnaire Module (QLQ-CR38) and Short Form 36 were the commonly used instruments to assess QoL in this review and most of the instruments included psychological, physical, social and functional aspects. Younger colorectal cancer patients had poorer quality of life when compared to elderly patients. Colorectal cancer also had a greater impact on quality of life outcomes in women when compared to men. The evidence generated from this systematic review will assist in the provision of information to develop effective intervention strategies to enhance quality of life and well-being for patients with colorectal cancer and to alleviate and/or prevent a worsening of the symptoms. A pre and post surgery psychosocial assessment should be part of the routine health examinations for early detection of psychosocial problems in patients with colorectal cancer. Future research is needed to explore further the factors that impact the quality of life of patients with colorectal cancer with focus on problems like depression, and bowel symptoms. Psychosocial factors have a great impact on patients' perceived quality of life. There is a need to develop interventions such as psychoeducation and self-management programme to help those newly diagnosed cancer patients and long-term cancer survivors.