Developing T cells diverge to several different effector classes, identified by their ability to express different set of genes. Aside from the genes encoding components of the TCR/CD3, there are many others that are activated and/or inactivated during T-cell development, but the functions of most of them are not yet defined. Despite the significant progress made, several fundamental aspects of the major steps of T-cell differentiation remains unclear. Thus, while long ago it was realized that the thymus is a central organ for the development of functionally competent T lymphocytes, it appears clear today that ectopic T-cell differentiation can also take place. In this article we review some of the molecules implicated in T-cell development and discuss some of the pathways that lead to mature T cells from precursors, both intra- and extra-thymically, as well as their implications in the acquisition of self tolerance.