In host–parasite systems, protein–protein interactions are key to allow the pathogen to enter the host and persist within the host. The study of host–parasite molecular communication improves the understanding the mechanisms of infection, evasion of the host immune system and tropism across different tissues. Current trends in parasitology focus on unraveling host–parasite protein–protein interactions to aid the development of new strategies to combat pathogenic parasites with better treatments and prevention mechanisms. Due to the complexity of capturing experimentally these interactions, computational approaches integrating data from different sources (mainly “omics” data) become key to complement or support experimental approaches. Here, we focus on the application of experimental and computational methods in the prediction of host–parasite interactions and highlight the potential of each of these methods in specific contexts. Get the chapter here!