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Anthelmintic resistance now poses problems to sheep farmers throughout the world. In some Southern hemisphere countries multiple resistance has reached levels which make sheep farming non-sustainable. Evidence from studies in the UK and Europe suggests (a) that the selection process occurs over a longer time frame than in Southern tropical/temperate regions and (b) that for some of the key ovine species little or no reversion to susceptibility may occur for many years after the withdrawal of the selecting agent. The dynamics of the selection process are influenced by a number of host, parasite, drug, management and environment-dependent factors. Recent mechanistic studies on resistance against avermectins and milbemycins (AM) suggest that there may be a number of mechanisms associated with resistance at the different target sites for these drugs. Within Europe endectocides within the AM drug group have now become the crucial element in strategies aimed at controlling important diseases such as sheep scab and nematodoses. Given that there is little likelihood of a series of novel action compounds emerging in the immediate future to replace this family the conservation of efficacy of the AM group should be accorded the highest priority for research in this area.