The most common treatments for infectious diseases target the invading pathogen. The efficacy of such an approach may, however, be countered by the possibility of the development of resistance to a pharmacophore, through mutation(s) in pathogen molecules required for activity. Given the fact that pathogens exploit host factors in order to grow in an otherwise hostile environment, one possible way to circumvent the emergence of resistance is to develop drugs that target non-essential host factors hijacked by the pathogen, rather than the pathogen’s own molecules. Such solutions are already being developed for various viral and bacterial pathogens, but much less has been achieved with infections caused by protozoan parasites, as is the case of Plasmodium. Here, we highlight recent progress in host target-based anti-viral and anti-bacterial approaches and discuss possible host targets that may be used for anti-malarial interventions. Host molecules that play a role during either the liver or the blood stage of Plasmodium infection are outlined and their potential merits as anti-malarial targets are discussed.