Cell fate specifications during T lymphocyte differentiation result from the orchestrated expression of developmentally regulated genes. Furthermore, epigenetic processes that result in a heritable chromatin structure are required for the maintenance of gene expression programs within cells. More and more is known about the basic mechanisms of T cell development and their diversification into various peripheral T cell subsets. Recent research has begun to provide insight into the interactive network of transcription factors as critical regulators of T lymphocyte differentiation. In the past years several members of the BTB domain-containing family of zinc finger proteins (BTB-ZF) have been described to be important for the development and function of hematopoietic cells, and also to contribute to malignant hematopoiesis. This review will provide a brief overview about the role of BTB-ZF proteins during thymocyte development and T cell function.