Arthropods have well adapted to the vast array of chemicals they encounter in their environment. Whether these xenobiotics are plant allelochemicals or anthropogenic insecticides one of the strategies they have developed to defend themselves is the induction of detoxification enzymes. Although upregulation of detoxification enzymes and efflux transporters in response to specific inducers has been well described, in insects, yet, little is known on the transcriptional regulation of these genes. Over the past twenty years, an increasing number of studies with insects have used advanced genetic tools such as RNAi, CRISPR/Cas9 and reporter gene assays to dissect the genomic grounds of their xenobiotic response and hence contributed substantially in improving our knowledge on the players involved. Xenobiotics are partly recognized by various ?xenobiotic sensors? such as membranebound or nuclear receptors. This initiates a molecular reaction cascade ultimately leading to the translocation of a transcription factor to the nucleus that recognizes and binds to short sequences located upstream their target genes to activate transcription. To date, a number of signaling pathways were shown to mediate the upregulation of detoxification enzymes in arthropods and to play a role in either metabolic resistance to insecticides or hostplant adaptation. These include nuclear receptors AhR/ARNT and HR96, GPCRs, CncC and MAPK/CREB. Recent work reveals that upregulation and activation of some components of these pathways as well as polymorphism in the binding motifs of transcription factors are linked to insects? adaptive processes. The aim of this mini-review is to summarize and describe recent work that shed some light on the main regulatory routes of detoxification gene expression in insects.