The extraterritorial reach of unilateral sanctions regimes could theoretically be neutralized through the implementation of blocking statutes and regulations. These instruments seek to protect domestic operators from the disproportionate extension of United States’ enforcement jurisdiction. Yet their efficacy is highly contested insofar as they do not effectively shield domestic operators from so-called “secondary sanctions”. This observation is exemplified by the resumption of US extraterritorial sanctions against Iran in 2018. Various factors lead to this conclusion. The chapter points out the structural deficiencies of blocking statutes and regulations for neutralizing the reach of extraterritorial sanctions. It also analyses the behaviour of involved parties towards such instruments: first, US enforcement authorities who impose secondary sanctions despite the existence of a blocking law; second, domestic operators whose economic interests may precipitate the non-enforcement of the blocking law; third domestic courts and tribunals who may give precedence to such economic interests over the enforcement of a blocking law.