Host–parasite interaction may enable a host to defend itself effectively against parasites. If some of the genetic variance for fitness is derived from additive genetic variance, the host population may adapt to fight the onslaught of parasites. Launching a defense mechanism only when challenged by a parasite or only under circumstances when there is a higher chance of developing sickness is an economical approach of shielding against parasitic invaders. Gene rearrangement that inserts a new variant-specific glycoprotein (VSG) gene into the expression site alters the expression level of the existing VSG gene. Many infecting parasites cover themselves with host/host-like elements, such as proteins or glycoconjugates, therefore avoiding their recognition as foreign objects by the host immune system. Most parasites have a complicated biology encompassing several developmental stages or variants that display diverse antigenic profiles, so indirectly driving the host to produce multifarious stage-specific immune responses. To escape complement-mediated killing, parasites have evolved several strategies including the expression of orthologs of human proteins or acquisition of the host complement regulating proteins onto the parasite surface to restrict complement activation and/or the expression of parasite proteins that bind to complement components to limit the complement protein functions.