Many species of different protozoan groups spend all or parts of their life cycles as parasites within vertebrate hosts, including humans. The host response and the parasites' escape strategies, which are as different as the niche within the host organism, will be discussed using the examples of Toxoplasma, Cryptosporidium, Leishmania, Plasmodium and Trypanosoma. Depending on the parasite's life cycle, the severity of the disease and the kinetics of dissemination, different diagnostic methods are applied. Once established, the different parasite species have a remarkable ability to suppress and/or divert the host's immune response so that the infection will ultimately be controlled and tolerated, but not eliminated. This delicate equilibrium is easily disturbed by concomitant infections or immunosuppressive treatment. In the case of HIV infection, some of these protozoan parasitic infections, notably toxoplasmosis, cryptosporidiosis and visceral leishmaniasis, will develop as opportunistic infections with an often fatal outcome. However, this aggravation is not observed in infections with Plasmodium or Trypanosoma. These complex modifications of the host's immune response by a concomitant infection or immunosuppressive treatment dramatically change the physiopathology, while having no effect on serological and PCR diagnostic results. This demands novel diagnostic tools which are more appropriate for these situations.