In this article, George Hani and Alan Horowitz discuss the next steps after the Supreme Court's unanimous decision in Mayo Foundation for Medical Education and Research v. United States, which captured the attention of tax practitioners as the court provided a significant victory for the IRS regarding deference owed to Treasury regulations. Since the court's decision in Mayo, several circuit courts have addressed deference questions not presented in Mayo in the context of asserted overstatements of basis and the application of the six-year statute of limitations under Code sections 6501 and 6229. The article discusses how these cases – one of which (United States v. Home Concrete & Supply) has been accepted for review by the Supreme Court – will further illuminate these deference issues and the impact that issuance of a Treasury Regulation can have on a dispute that appeared to have been settled by a judicial decision. In particular, these cases should provide guidance on an important issue not addressed in Mayo relating to the retroactive effect of deferred-to regulations.