Development of resistance to anthelmintic drugs is an increasing problem that decreases the productivity of livestock and threatens the success of treatment in humans. It is essential to understand the mechanisms in the development of resistance so that alternative treatment strategies can be developed. Changes in genes or in gene expression in response to drugs enable the organism to survive treatment and might reflect evolution in a toxic environment in which drug resistance leads to 'survival of the fittest'. Here, we review knowledge of resistance mechanisms, focusing on changes in drugs (identified by single-nucleotide polymorphisms), the involvement of transport proteins and drug efflux that prevent the drug from reaching the target, and the role of detoxification mechanisms that modify the drug.