Purpose of Review <p>The aim of this review is to highlight the relevance of cell rigidity changes in malaria pathology while exploring the possible targets related to these changes in drug discovery.</p> Recent Findings <p>Recently, blocking signaling routes related to deformability during <i>Plasmodium</i> infection was shown to inhibit the progression of asexual forms of the parasite and block the transmission of gametocytes.</p> Summary <p>This literature review revealed that changes in the stiffness of the erythrocyte membrane play an important role in <i>Plasmodium</i> invasion and that the changes that continue to occur as the parasite develops within the cell also play a role in the pathology. In the case of sexual forms, this plays an even more crucial role in enabling mature sexual forms to return to the bloodstream and escape from bone marrow sequestration, allowing transmission to occur. These findings provide evidence of the potential impact of blocking the targets involved in these regulatory pathways as a strategy for drug discovery and blocking parasite transmission.</p>