Chagas disease, caused by the protozoa Trypanosoma cruzi, is endemic from Latin America and is considered a neglected tropical disease (NTD). An estimated 8 million people worldwide are infected, the country with the highest disease burden being Bolivia. Chagas disease has overcome borders, and it is no longer restricted to endemic countries. Nowadays, it can be found in the Unites States, Canada, Europe, Japan, and Australia, mainly due to mobility of population. Spain ranks second only to the United States in the list of countries receiving migrants from Latin America, and it is the European country with the highest prevalence of Chagas disease, therefore posing a challenge in terms of public health [1]. T. cruzi transmission is feasible in vector-free world regions. The main nonvectorial routes are congenital transmission, blood transfusion, and solid organ transplant. In fact, in Europe as well as in other nonendemic areas, there have been several cases of vertical transmission of T. cruzi and also transmission through infected tissue or blood products. Many nonendemic countries have not yet established official guidelines to avoid these routes [1], [2]. Mandatory screening of blood donors at risk for T. cruzi infection has been implemented since October 2005 in Spain targeting donors born in endemic areas, those whose mothers were born in endemic areas, and people who received blood transfusions in endemic areas [3]. Although not included in the Royal Decree, many blood banks also screen individuals who have resided in endemic areas for more than 2 months. In Spain, there is a national law that regulates the activity of tissue banks; moreover, the Spanish Society of Tropical Medicine and International Health has published a document in order to establish the guidelines to be followed in case a potential donor or a tissue or organ recipient could be affected by Chagas disease [4]. According to the recommendations of the WHO experts on the control and management of congenital Chagas disease, screening should be carried out during pregnancy to detect mothers who carry the infection and are at risk of transmitting the infection to their offspring. Furthermore, the WHO states that cases of congenital T. cruzi infection should be treated as soon as the diagnosis is confirmed using benznidazole or nifurtimox [5]. In Spain, systematic detection of congenital infection is not performed at the national level [1]; only two regions (Autonomous Community of Valencia and Catalonia) have a specific protocol. Currently, several scientific groups have drafted a clinical guide, which will be published shortly, about diagnosis, follow-up, and treatment of pregnant women and children with Chagas disease. Regarding treatment of infected newborns, the WHO recommendations are followed [5], using benznidazole as the first-line treatment option for Chagas disease in children and adults in Spain. Stocks of this drug ran out at the end of last year, which will result in Chagas disease becoming a NTD also in developed countries [6]. Until March 2012, this drug was only produced by the Brazilian state-owned laboratory LAFEPE. At that moment, the drug started to be produced also in Argentina through a private-public partnership led by Fundacion Mundo Sano. Benznidazole is available in Spain for all patients from the second half of November 2012. Estimating the burden of Chagas disease in nonendemic countries is crucial in order to plan preventive measures and to determine the resources for screening and treatment. Estimates are normally calculated according to the number of Latin Americans registered in each country and to the infection rates in their countries of origin. Thus, it is assumed that the prevalence of the infection in the host country is the same as that in the country of origin, this being the main limitation for achieving accurate estimations. In the past recent years, estimates on the expected number of migrants with T. cruzi infection have been carried out in Spain. The last one yields a figure of 48,000–86,000 cases, based on the Bolivians' infection rates of three studies performed only in two regions of Spain [7]. Being aware of the heterogeneous distribution of immigration, studies performed in different geographical regions of Spain were taken into account in this article in order to reach a comprehensive approach.