Vector-borne diseases are an increasing cause of death and suffering worldwide. Efforts to control these diseases have been focused on the use of chemical pesticides, but arthropod resistance (whether physiological, biochemical, or behavioral) to pesticides is now an immense practical problem. The pharmacokinetic interactions of pesticides with arthropods, mechanisms of resistance, and the strengths and shortcomings of different resistance test methods are briefly reviewed. Using malaria control as an example, the differences between the efficacy of insecticide-sprayed houses in reducing malaria transmission, and the actual effect of such treatments on vectors are discussed. Reduced malaria transmission as a result of spraying house walls occurs through some combination of killing vectors that land on sprayed walls (insecticidal effect) and by preventing vectors from entering or remaining inside long enough to bite (behavioral effects). Both insecticidal and behavioral effects of insecticides are important, but the relative importance of one versus the other is controversial. Field studies in Africa, India, Brazil, and Mexico provide persuasive evidence for strong behavioral avoidance of DDT by the primary vector species. This avoidance behavior, exhibited when malaria vectors avoid insecticides by not entering or by rapidly exiting sprayed houses, should raise serious questions about the overall value of current physiological and biochemical resistance tests. The continued efficacy of DDT in Africa, India, Brazil, and Mexico, where 69% of all reported cases of malaria occur and where vectors are physiologically resistant to DDT (excluding Brazil), serves as one indicator that repellency is very important in preventing indoor transmission of malaria. This experience with DDT has implications for future control efforts because pyrethroids also stimulate avoidance behaviors in arthropods. Each chemical should be studied early (before broad-scale use) to define types of action against vector species by geographic area, especially for impregnated bed net applications. The problems for vector control created by use of insecticides in agriculture and the potential for management of resistance in both agriculture and vector-borne disease control are discussed.