Patients with a suspected myocardial infarction (MI) in the setting of a left bundle branch block (LBBB) present a unique diagnostic and therapeutic challenge to the clinician. A diagnosis of MI with electrocardiogram (ECG) is especially difficult in the setting of LBBB because of the characteristic ECG changes caused by altered ventricular depolarization. The Sgarbossa criteria1 were first introduced over 20 years ago to improve the diagnostic accuracy for MI in the presence of LBBB; others have subsequently modified the criteria to improve sensitivity.2 Here we review the pathophysiology of LBBB in MI, discuss current guidelines, and highlight evolving paradigms for the diagnosis and treatment of suspected MI in patients with LBBB.