Critically ill patients with disseminated strongyloidiasis may not be candidates for oral treatment. We report four patients with disseminated strongyloidiasis, believed to be unable to absorb oral therapy, who were treated with ivermectin by rectal and/or subcutaneous administration. Obtaining subcutaneous ivermectin and dosing it appropriately is a challenge. These cases underscore the need for improved access to subcutaneous ivermectin and more pharmacological data to guide use of this treatment approach.