Insect cytochrome P450s are known to play an important role in detoxifying insecticides and plant toxins, resulting in the development of resistance to insecticides and facilitating the adaptation of insects to their plant hosts. Insect P450s are associated with enhanced metabolic detoxification of insecticides in insects, as evidenced by the increased levels of P450 proteins and P450 activities that result from constitutively transcriptional overexpression of P450 genes in insecticide resistant insects, and some insect P450 genes can be induced by exogenous and endogenous compounds. Both constitutively increased expression (overexpression) and induction of P450s are thought to be responsible for increased levels of detoxification of insecticides. This chapter reviews strategies for the isolation of cytochrome P450s from house flies and the characterization of their possible importance in insecticide resistance.