Understanding the diversity of insect responses to chemical pressures (e.g. plant allelochemicals and pesticides) in their local ecological context represents a key challenge in developing durable pest control strategies. To what extent do the resistance mechanisms evolved by insects to deal with the chemical defences of plants differ from those that have evolved to resist insecticides? Here, we review recent advances in our understanding of insect resistance to plant chemicals, with a special emphasis on their underlying molecular basis, evaluate costs associated with each resistance trait, and discuss the ecological and evolutionary significance of these findings.