Innate immune cells play a crucial role in the front line of defence protecting the human body against pathogens and harmful substances. One particular subtype of innate immune cells are innate lymphocytes. These have the ability to either directly eliminate cells or efficiently coordinate the advanced immune response during infections. In steady state innate lymphocytes are important for immune tolerance, immune surveillance, maintenance and repair of damaged tissues. Dysregulation of their function leads to chronic inflammation, autoimmune disease and cancer, which makes it important to investigate the essential factors that orchestrate innate lymphocyte development and functionality. Maho Nagasawa describes the transcription factors involved in the development of various types of human innate lymphocytes.