This review examines the challenges of segregating biopharmed crops expressing pharmaceutical or veterinary agents from mainstream crops, particularly those destined for food or feed use. The strategy of using major food crops as production vehicles for the expression of pharmaceutical or veterinary agents is critically analysed in the light of several recent episodes of contamination of the human food chain by non-approved crop varieties. Commercially viable strategies to limit or avoid biopharming intrusion into the human food chain require the more rigorous segregation of food and non-food varieties of the same crop species via a range of either physical or biological methods. Even more secure segregation is possible by the use of non-food crops, non-crop plants or in vitro plant cultures as production platforms for biopharming. Such platforms already under development range from outdoor-grown Nicotiana spp. to glasshouse-grown Arabidopsis, lotus and moss. Amongst the more effective methods for biocontainment are the plastid expression of transgenes, inducible and transient expression systems, and physical containment of plants or cell cultures. In the current atmosphere of heightened concerns over food safety and biosecurity, the future of biopharming may be largely determined by the extent to which the sector is able to maintain public confidence via a more considered approach to containment and security of its plant production systems.