Protozoan pathogens have evolved countermeasures to avoid immune clearance and prolong the period of infection in their vertebrate hosts. The type and degree of immune escape strategies depends on the in vivo 'lifestyle' the pathogen has adopted. Here we describe how parasites use different strategies to coordinate their expression of phenotypic variation, which is used in many cases to fool the immune system, or to successfully invade new host cells. Recent insights using modern molecular biology techniques show that this is achieved via a coordinated manner of action of different epigenetic factors such as histone marks, subnuclear localization, or novel unknown mechanism(s). This emerging field may have an enormous impact on disease therapy.