Lymphocyte development is initiated from hematopoietic stem cells and can be divided into multiple phenotypically distinct stages. Transcription factors play important roles in programming the developmental process of lymphocytes. Recent studies have identified key roles of several orphan nuclear receptors in T lymphocyte development. The orphan nuclear receptor RORgamma has been shown to promote thymocyte survival by activating the expression of antiapoptotic protein Bcl-x(L). RORgamma is also required for the development of lymph nodes and Peyer's patches. The orphan receptors Nur77 and Nor1 are involved in TCR-mediated cell death and thymocyte-negative selection. These studies provide novel insights into the molecular mechanisms of T lymphocyte development.