Current strategies for the treatment of hereditary angioedema (HAE) include targeted inhibition or antagonism of the contact system, which is dysregulated in HAE patients by a C1 esterase inhibitor deficiency. Ecallantide, a plasma kallikrein inhibitor, and icatibant, a selective bradykinin-2 receptor antagonist, have recently been evaluated in clinical studies for the treatment of acute HAE attacks. Both drugs have demonstrated evidence of efficacy and safety in treating acute HAE episodes, with ecallantide approved for use in the United States and icatibant approved for use in Europe. As therapeutic options for HAE expand for both for prophylactic and acute treatment strategies, a number of patient-specific and drug-specific factors have emerged as important considerations when developing individualized HAE management plans. Optimization of HAE therapy will require further integration of new therapies into the current treatment paradigm.