The combination of molecular biology, epidemiology, virology, evolutionary and population genetics has enabled us to understand the delicate interplay between HIV and the CCR5-Delta32 HIV resistance allele. We here review and collect from the different approaches to show how they can be combined to elucidate the interaction between host and pathogen genetics in this system. We will present an overview of the normal role of CCR5, its involvement in HIV, the molecular biology of the CCR5-Delta32 allele and its probable origins. By focusing on this well-documented and important system we hope to demonstrate the power that such a "holistic" approach might offer in the study of infectious diseases.