For nearly a half century, cockroaches have been recognized as a major cause of asthma morbidity in the urban, inner-city environment. Several cockroach-produced allergens have been identified and characterized, and a few have been produced as recombinant proteins. Recent research has moved beyond clinical, patient-based investigations to a more entomological perspective that addresses the production, physiological regulation, and developmental expression of cockroach allergens, thus providing insight into their functional biology and their relationship to current cockroach control strategies. Although successful removal of cockroach allergens from the infested environment has been difficult to accomplish with remedial sanitation, large-scale reductions in cockroach allergens below clinically relevant thresholds have recently been realized through suppression of cockroach populations. Here we review the current understanding of cockroach allergen biology and the demographics associated with human exposure and sensitization. We also critically evaluate allergen mitigation studies from an entomological perspective, highlighting disparities between successful and failed attempts to lessen the cockroach allergen burden in homes.