Several important issues must be considered when performing any vaccination in areas with high prevalence of geohelminths. Immunization of populations infected with geohelminths could be sub-optimal if the immune background is not taken into consideration. Immune modulation and deworming might be essential for effective protective vaccination. In addition, further animal models and clinical studies addressing these issues are required. Underscoring the importance of these issues, a recent report has highlighted several vaccination studies in which nematode-infected mice or pigs failed to mount efficient protective immune responses.