The haploid social soil amoeba Dictyostelium discoideum has been established as a host model for several pathogens including Pseudomonas aeruginosa, Cryptococcus neoformans, Mycobacterium spp. and Legionella pneumophila. The research areas presently pursued include (i) the use of Dictyostelium wild-type cells as screening system for virulence of extracellular and intracellular pathogens and their corresponding mutants, (ii) the use of Dictyostelium mutant cells to identify genetic host determinants of susceptibility and resistance to infection and (iii) the use of reporter systems in Dictyostelium cells which allow the dissection of the complex host-pathogen cross-talk. The body of information presented in this review demonstrates that the availability of host cell markers, the knowledge of cell signalling pathways, the completion of the genome sequencing project and the tractability for genetic studies qualifies Dictyostelium for the study of fundamental cellular processes of pathogenesis.