NK cells sit at the crossroads of innate and adaptive immunity and help coordinate tumor immunosurveillance and the immune response against pathogens. Balancing signals to NK cell precursors is crucial for their early development, when transcription factors compete to specify the different lymphocyte subsets. Despite an elaborate schema for NK cell development and differentiation, several major issues remain to be addressed, such as identifying the sites for NK cell maturation and defining the peripheral NK cell niche.