To understand how the immune system manages to disarm potentially harmful T cells with reactivity against self-antigens, many immunologists have turned to model systems in which transgenic expression of TCRs, foreign antigens, or both, allows visualization of otherwise undetectable mechanisms. Recent data have offered several new insights into the variables that dictate the mechanism for tolerance employed by peripheral T cells. Some of these mechanisms can also dampen ongoing immune responses against foreign antigens and provide a strikingly powerful supplement to the primary mechanism of tolerance, thymic clonal deletion.