The present strong emphasis on gross organ pathology (liver, kidneys, bladder) in schistosomiasis needs to be replaced with a more balanced view of the disease that also takes into account systemic symptoms that are less easy to assess, such as retarded growth, cognitive development and the effect of continuing low-level blood loss. Access to better estimates of disease burdens, morbidity and mortality is delivering results that bring into question the wisdom of downgrading the impact of the disease. In this scenario, the simplistic approach of exclusive drug treatment might not be sufficient and, in the worst-case scenario, might even exacerbate pathology. To meet this challenge, the repositioning of vaccines within the totality of disease control through the combined use of chemotherapy and vaccination is recommended as the basis for a novel, more-versatile approach to control. Studies on human correlate responses in endemic areas have opened the way to assess the protective value of specific antigens through the cytokine responses and antibodies they elicit. Moreover, vaccine formulations based on novel adjuvants could improve the final outcome through selective manipulation of the immune response. Thus, the tools of vaccine-linked chemotherapy are in principle already available and could shortly be put to the test in clinical trials.