Neonatal tolerance of alloantigens was described in mice nearly half a century ago, but unfortunately, the translation of these early findings into the clinical arena proved to be much more challenging than was first anticipated. However, the past decade has seen considerable progress in our understanding of the mechanisms that contribute to transplantation tolerance in experimental models. This review outlines our current understanding of the mechanisms of allograft tolerance, emphasizing the complementary roles of deletion and regulation of alloreactive T cells.