The enteric nervous system, also referred to as ‘the brain of the gut’, is important for gut functioning. In recent years, it has become evident that neurons can influence cancer, but how the brain of the gut influences colorectal cancer has hardly been investigated. This thesis focussed on the brain of the gut and its role in the development and progression of colorectal cancer. In addition, available models to study the brain of the gut were evaluated, with a focus on validating and improving these models for biomedical research. This research shows that neurons in the gut can influence colorectal cancer by sending signals to colorectal cancer cells on the one hand, and by influencing the immune system on the other hand.