Pesticide resistance is a long-standing and increasing concern for global food security. The spider mite Tetranychus urticae is a cosmopolitan key crop pest with a great ability to evolve acaricide resistance. To develop efficient resistance management strategies, it is crucial to understand the genetic basis of resistance. In this thesis, two novel mutations were identified in the mitochondrial cytochrome b Q0 site of T. urticae: G132A and G126S+A133T. Several lines of evidence were provided for the causal role of these mutations in resistance to the Q0 inhibitor acaricides bifenazate and acequinocyl. In addition, G132A was linked to several fitness penalties in resistant mites. Pyflubumide is a novel carboxanilide acaricide that inhibits mitochondrial complex II of spider mites. In a thorough resistance risk assessment of this compound, low-to-moderate levels of cross-resistance between cyenopyrafen and pyflubumide was detected in the JPR strain. This strain was subsequently selected for higher levels of pyflubumide resistance under two different laboratory selection regimes, resulting in two highly resistant strains, JPR-R1 and JPR-R2. Several steps were taken to characterize the mechanisms underpinning pyflubumide resistance. Target-site insensitivity was not detected in the resistant mites. Synergism bioassays and transcriptomic analysis strongly suggested that cytochrome P450 monooxygenases are involved in pyflubumide resistance. Classic genetic crosses revealed that the resistance is polygenic with an incomplete recessive mode of inheritance. A high-resolution BSA genetic mapping approach uncovered three QTL associated with pyflubumide resistance, which contained CYP392A16, a cluster of CYP392E genes, and cytochrome P450 reductase (CPR). CYP392A16 was functionally expressed and in vitro assays showed that CYP392A16 N-demethylates the toxic carboxamide form of pyflubumide to a non-toxic compound. We identified copy number variation at the CPR locus as the likely causal structural variant underpinning the different transcription levels of CPR. All results were discussed in light of existing knowledge on the resistance mechanisms and management in T. urticae and other arthropod pests.