It is not widely appreciated that mammals can be venomous in the manner of snakes and lizards. However, it was first demonstrated scientifically 50 years ago in the case of the American short-tailed shrew. Subsequently, similar evidence has been obtained from European shrews and the Haitian solenodon, but research in this area has been almost completely neglected for the last 20 years. In complete contrast to what has been learned about other animal venoms, the identity and mode of action of mammal venom toxins are still unknown. This review draws attention once more to the pioneering work undertaken in the 1940s and 1950s, exploring in more detail than hitherto why the implications of mammal venom are just as important as the chemistry and pharmacology of the phenomenon itself.