Thirty years of control of the mosquito Culex pipiens using organophosphate insecticides (OP) has selected for OP-resistance alleles on a world-wide scale. As reviewed here, studies at the levels of gene and population allow identification of the main forces driving this process of adaptation. Three loci are involved in OP-resistance in C. pipiens. For two of these, adaptive mutations were found to be rare events, such that the ubiquitous distribution of certain resistance alleles could only be explained as deriving from a single origin by mutation followed by extensive migration. Population structure analyses confirmed that long-distance migration is frequent. Thus, different resistance alleles could accumulate and compete within populations soon after their origin by mutation. The different selection pressures acting on these alleles, i.e. their selective advantage in the presence of OP and their disadvantage (resistance cost) in absence of OP, were also analysed. Substantial differences in resistance cost among alleles present within the Mediterranean area were discovered. Long-term surveys of Mediterranean populations confirmed the pivotal importance of resistance cost in shaping the evolution of this adaptive polymorphism. Some hypotheses on the functional links between the nature of the initial mutation events and the subsequent evolution of polymorphism are discussed.