The most important progress in immunology in the last decade is the description of regulatory lymphocytes, among which Treg cells and regulatory NKT cells are much attractive to not only immunologists but also almost all biomedical researchers. Meanwhile, it is noted that NK cells are not only "Killers" but also regulate innate and adaptive immunity, especially in early stage, by secreting cytokines and cell-cell contact. In this review, we are going to briefly summarize the progresses in regulatory lymphocytes including T cells (Treg, Tr1, Th3), NKT cells and NK cells, and then extensively introduce the positive regulatory function of NK cells in both normal immune response and in disease condition (tumor, infection and autoimmunity), and finally, to focus on the most latest progression in the negative regulatory effects of NK cells on normal and pathogenic immune response. In conclusion, we speculate that a "regulatory NK (NK-reg)" cell subset exist and need to explore. Cellular & Molecular Immunology. 2006;3(4):241-254.