The term “magic bullet" was chosen to explain how a drug kills the pathogen with a greater affinity and
specificity to its target without effecting its orthologue in human. The ideal parasite target is a molecule
essential for its viability, growth, proliferation, and differentiation. The majority of commonly administered
anthelminthics target either neuromuscular elements, or metabolic pathways. On the other hand, genomics
studies combined with transcriptome analyses revealed advanced information in understanding hostparasite
interactions that yielded clues for new strategies in identification of new parasite targets and
designing novel inhibitors. In fact, next generation sequencing technology provides unique opportunities
to understand parasites molecular biology and their role in parasite-host interactions. Besides, drug
repurposing is a promising approach to expand the pool of molecules with potent inhibitory activity against
a specific parasite target. The present review aims to highlight the proposed potential helminth drug targets
with special emphasis on the major tropical diseases such as schistosomiasis, hydatid cyst, lymphatic
filariasis, onchocerciases and soil transmitted diseases. The review also highlights hypothesized potential
targets for future development of novel anthelminthics utilizing aminoacyl-tRNA synthetase and the 20S core
proteasome, as well as new strategies targeting parasitic response to overcome host mechanistic target of
rapamycin.