Ascaris infections remain major global public health problems despite the wide availability of cheap, effective anthelminthic drugs. An improved understanding of host susceptibility to Ascaris infection may suggest new approaches for targeting available drugs more effectively, or may suggest novel targets for drug development efforts. This chapter explores our current understanding of the underlying genetic architecture of susceptibility to Ascaris infection. The past and potential future uses of different types of genetic approaches, from quantitative genetic studies of heritability, to gene localization, to sequencing of functional variants, are explored. The field of human complex disease genetics is moving rapidly as a result of both technological and theoretical advances. State-of-the-art genetic techniques promise to yield new insights which will dramatically improve our understanding of the determinants of differential host susceptibility to Ascaris infection.