The incidence of colorectal cancer (CRC) in the Middle East is increasing, especially among those younger than 50 years. Risk factors including obesity, sedentary lifestyle, and dietary changes are associated with the epidemiologic shift and are a result of socioeconomic changes happening in the region. Worldwide, CRC screening is associated with decreased incidence and mortality of CRC, but screening uptake is still low in the Middle East because of cultural barriers and lack of awareness; in addition, most countries do not have national screening programs. Knowledge of CRC screening and participation rates vary among different countries, but overall they are low. Both primary and secondary prevention approaches are needed in the Middle East, and cost-effectiveness is important in choosing screening modalities. Although colonoscopy is considered the most robust screening method, stool-based testing may be an acceptable screening strategy in resource-limited settings, and focusing on high-risk individuals such as those with hereditary CRC might be the most cost-effective strategy. In addition to financial limitations in many countries in the Middle East, human displacement places an extra toll on cancer control strategies in the region.