<p>Schistosomiasis, a parasitic disease caused by <i>Schistosoma</i> species, affects millions of people worldwide. This review explores the therapeutic challenges of schistosomiasis, focusing on the mechanisms of action of current treatments and their limitations. Praziquantel, the standard therapy, induces lesions and muscle contractions in the parasites, thereby facilitating their clearance by the host immune system. However, the biological complexity of schistosomes and their ability to modulate the immune response present hurdles to sustained treatment efficacy. Challenges include the emergence of resistance, adverse side effects, and inconsistent cure rates. Additionally, the remarkable longevity of schistosomes—spanning years to decades—complicates the evaluation of treatment outcomes. Addressing these issues, requires ongoing surveillance, research into novel therapeutic agents, and an integrated approach that combines medical interventions with preventive measures. This paper underscores the importance of understanding schistosome biology and advocates for comprehensive strategies to improve the management and control of this debilitating parasitic infection.</p>