The fate of stem cells, such as neural stem cells and hematopoietic stem cells, depends on strictly regulated signaling events including activation of nuclear receptors, resulting in subsequent gene induction. Recently, we demonstrated that PPARγ, a ligand-activated nuclear receptor, plays an important role in regulating the proliferation and differentiation of murine neural stem cell (NSC). NSC prepared from heterozygous PPARγ-deficient mouse exhibited a slower growth rate compared with that of wild-type mouse, which was also demonstrated in PPARγ-knockdown NSC that was generated by the lentiviral-vector-mediated RNA interference approach. These studies have important implications for understanding central nervous system functions and developing a therapy for neurodegenerative disorders. In this review, recent findings on stem cell biology, especially focusing on nuclear receptors in NSCs, including our current study, will be discussed.