More than 50,000 refugees are resettled to the United States annually, many from areas highly endemic for parasites. Some of these infections present little clinical consequence after migration, but others are responsible for morbidity and mortality. The Centers for Disease Control and Prevention has issued predeparture presumptive treatment and postarrival medical guidelines for the management of parasites. Although these guidelines are evidence based, there remain significant challenges to presumptive treatment programs in refugees. Gaps in the evidence continue; resettling populations are continually changing, thus altering the epidemiology; and there are logistical and cost barriers to fully implementing recommendations. This article will review the evolution and status of current guidelines, as well as identify gaps and challenges to full implementation. It is imperative for clinicians serving this population to be familiar with interventions received by refugees, since previous treatment will impact screening, diagnostic evaluation, and treatment decisions.