From the early days of natural killer (NK) cell research, it was clear that MHC genes controlled the specificity of mouse NK cell-dependent responses, such as the ability to reject transplanted allogeneic bone marrow and to kill tumour cells. Although several mechanisms that are involved in this 'education' process have been clarified, most of the mechanisms have still to be identified. Here, we review the current understanding of the processes that are involved in NK cell education, including how the host MHC class I molecules regulate responsiveness and receptor repertoire formation in NK cells and the signalling pathways that are involved.