NK cells recognize foreign cells through a complex interaction between activating and inhibitory receptors for surface molecules on a target cell. Some of these target ligands belong to the family of polymorphic MHC class I molecules. The consensus has been that most of the receptors recognizing class I molecules are inhibitory and react with class I of the individual, in agreement with the “missing self” hypothesis. They therefore represent a new control mechanism to safeguard against autoreactivity of the NK cells. More recent studies, however, show that some of these receptors also can be activated by class I molecules, also allogeneic class I. This is particularly evident from a rat experimental model for NK alloreactivity, which is the focus for this review. The array of activating and inhibitory NK cell receptors for polymorphic class I molecules represent novel recognition systems within the innate immune system, and challenge our views on how the polymorphisms of the class I molecules have evolved to make cells identified as self or foreign by the immune system.