Roughly one in five patients with colorectal cancer develops peritoneal minimal residual disease after surgical resection, and about one in seven patients develops peritoneal carcinomatosis. By contrast with the vast body of research addressing haematogenous metastasis, little is known about the biology of peritoneal spread of colorectal cancer. The development of peritoneal carcinomatosis involves well-defined steps including cell shedding and transport, adhesion to the mesothelial layer, invasion of and proliferation into the submesothelial stroma, and potential access to the systemic circulation. In this Review, we summarise the molecular mechanisms and potential preventive measures associated with each step of the peritoneal metastatic cascade.