Genes of the major histocompatibility complex (MHC) have provided some of the clearest examples of how natural selection generates discordances between adaptive and neutral variation in natural populations. The type and intensity of selection as well as the strength of genetic drift are believed to be important in shaping the resulting pattern of MHC diversity. However, evaluating the relative contribution of multiple microevolutionary forces is challenging, and empirical studies have reported contrasting results. For instance, balancing selection has been invoked to explain high levels of MHC diversity and low population differentiation in comparison with other nuclear markers. Other studies have shown that genetic drift can sometimes overcome selection and then patterns of genetic variation at adaptive loci cannot be discerned from those occurring at neutral markers. Both empirical and simulated data also indicate that loss of genetic diversity at adaptive loci can occur faster than at neutral loci when selection and population bottlenecks act simultaneously. Diversifying selection, on the other hand, explains accelerated MHC divergence as the result of spatial variation in pathogen-mediated selective regimes. Because of all these possible scenarios and outcomes, collecting information from as many study systems as possible, is crucial to enhance our understanding about the evolutionary forces driving MHC polymorphism. In this issue, Miller and co-workers present an illuminating contribution by combining neutral markers (microsatellites) and adaptive MHC class I loci during the investigation of genetic differentiation across island populations of tuatara Sphenodon punctatus. Their study of geographical variation reveals a major role of genetic drift in shaping MHC variation, yet they also discuss some support for diversifying selection.