Takotsubo cardiomyopathy, also known as left ventricular apical ballooning syndrome and stress-induced cardiomyopathy, is typically characterized by transient systolic dysfunction of the apical and mid-segments of the left ventricle, in the absence of obstructive coronary artery lesions. Patients may present with symptoms and signs of acute coronary syndrome, and the provider is challenged to differentiate between these conditions. In this review, we guide the reader through the diagnostic pathway, focusing on differential diagnoses and diagnostic criteria for takotsubo cardiomyopathy.