What does it take to make a natural killer?

We know how B and T cells develop, what they 'see' and the receptors they 'see with'. By contrast, and despite an unprecedented increase in the number of receptors and ligands known to regulate the activity of natural killer (NK) cells, we still have many questions regarding how these cells develop. Nevertheless, we are beginning to understand the transcriptional programmes of NK-cell maturation and the role of the effector functions of NK cells in the regulation of immune responses. An improved knowledge of NK-cell development in mice and humans might be useful to harness the power of these natural killers in the clinic to fight autoimmune diseases, infection and cancer.