Prophenoloxidase activating proteinase (PAP) is a key proteinase in the process of activation of prophenoloxidase in several insect defense mechanisms. An immune challenge can induce proteins at the start of the prophenoloxidase activation cascade to activate the precursor of PAPs by proteolytic cleavage. The activated PAPs cause inactive prophenoloxidase to form active phenoloxidase (PO) and ultimately to produce toxic substances in order to kill foreign organisms, such as pathogens and parasites. This paper reviews the characteristics and structure of PAPs in insects, as well as their role in the prophenoloxidase-activating system, and discusses the regulation of PAPs in host insects by parasitoid wasps.