Plants contain proteins that are capable of inactivating ribosomes, commonly referred to as Ribosome Inactivating Proteins (RIPs). These particular plant proteins have received attention in biological and biomedical research because of their unique biological activities towards animals and human cells as cell-killing agents. Some of the best-characterised RIPs have been isolated from exotic plants, but they have also been found in cereals and other food crops. Cereals contain, in general, RIPs in the endosperm protein pool: they share a high similarity with all the other RIPs retaining, however, characteristic features forming a distinct class which diversified significantly during evolution. They appear to be involved in quite different physiological roles, such as defence against pathogens and/or involved in regulatory and developmental processes. This review aims to provide a critical assessment to work related to cereal RIP with particular emphasis to the maize RIPs.