While feeding and breeding on decaying matter or feces, larvae and adults of the housefly (Musca domestica L.) ingest microorganisms and consequently serve as vectors for numerous pathogens. However, even though houseflies are constantly exposed to septic conditions—harboring microbes in their digestive tract and on their external surfaces—they are remarkably impervious to infection and disease. Microbial resistance may be mediated by physical barriers such as the cuticle or peritrophic matrix or by the activity of immune-responsive agents (microbicidal or microbistatic substances). While many studies have examined housefly-microbe symbiosis from the microbiological perspective, little is known about the immune defenses of the fly. The research presented here examined the interactions of houseflies and microbes by looking at the role of the housefly’s immune response in microbial symbiosis. We have cloned and identified three antimicrobial peptide (AMP) genes from the housefly: attacin, defensin and cecropin. Northern analysis of these AMPs showed differential expression in response to microbe “type” (Gram negative bacterium, Gram positive bacterium and broad spectrum antimicrobial, respectively) which is consistent with results seen previously in Drosophila. To begin to assess a functional role for these AMPs in the housefly’s resistance to microbial disease, their temporal expression was examined: 1. across life history (larva, pupa, young adult, old adult); and 2. in response to various microbes and nutritional states (as time course after exposure). These results, along with future studies, will reveal both strengths and vulnerabilities of the housefly immune system which possibly will lead to the development of new targets for pest control.