Twentieth century America was the site for many pandemic infectious diseases, including influenza, syphilis, and HIV/AIDS. As the federal government and citizens alike worked to combat these diseases, theatre artists of the day produced work that reflected the concerns and sensibilities of their communities in response to these public health threats. By examining these plays in the context of the diseases they address, a more complete picture of theatrical reactions to public health crises can be catalogued. This paper turns a critical and dramaturgical eye to Alice Rostetter’s The Widow’s Veil in the context of the 1918 influenza pandemic, Arnold Sundgaard’s Spirochete in the context of American Surgeon General Thomas Parran’s campaign for the eradication of syphilis, and Steven Dietz’s Lonely Planet in the context of later years of the AIDS crisis in America proper, in order to better explore the effect of pandemic infectious disease on the theatrical output of twentieth century American playwrights.