All living organisms are exposed to potentially harmful compounds which they can only survive if these compounds are detoxified rapidly. For herbivorous arthropods, these consist of plant defense compounds, but also pesticides used to protect our crops. Spider mites such as Tetranychus urticae are major crop pests with a remarkable ability to develop pesticide resistance. Understanding the mechanisms of resistance and host plant adaptation is important to maintain a sustainable plant production. Recently, the availability of a genome sequence in combination with newly developed genomic tools have revealed that ABC transporters and UDP-glycosyl transferases (UGTs) are associated with xenobiotic resistance, but they are not studied so far. Here, we will identify candidate causal genes that will be functionally expressed to study their substrate specificity and interactions with toxins. Reverse genetics (RNAi, CRISPR knockouts) will be applied to provide formal evidence of their role in xenobiotic resistance. A better understanding of the role of these new players in resistance will allow to better manage resistance and potentially devise alternative control strategies.