Colorectal cancer is a major cause of morbidity and mortality, and screening has been shown to reduce morbidity and mor-tality. This review highlights pertinent aspects of adherence to screening including the various options available and key concepts to consider in any systematic program. Persistent adherence, which is key to an efficacious screening program, is the compliance with repeated screening tests over a period of time. A “chain of survival” mindset emphasizes the step-wise, sequential and persistent approach to screening and is a helpful concept to drive the message of persistent adher-ence. A framework for the patient and physician interactions that support screening intervention is examined, and various factors that impact both patient and physician adoption and screening modality recommendations are reviewed. While systems-based approaches to screening have great utility in automation and monitoring in a surveillance program, some emerging data suggests that the human touch is still an essential driver for active participation in these programs. Fi-nally, the proportion of time concept is discussed as a useful index for monitoring persistent adherence in both individualsand populations.