RISBASEs are RNases with surprising biological actions, or unexpected physiological roles, in which they act as external factors that influence cell behaviour. There are RISBASEs involved in host defence, angiogenesis and the control of pollen fertility, and RISBASEs with antitumour and antispermatogenic actions. Here, Guiseppe D'Alessio describes these unusual roles for RNases, and speculates about the mechanisms underlying their actions.