Next-generation sequencing has become increasingly accessible and economical, making genome-wide studies routine for many species, including humans, model organisms, and domestic livestock. However, in the case of helminth parasites, there are still major practical challenges to the application of these approaches for genetic and population studies. Dozens to hundreds of individual parasites from multiple populations may need to be re-sequenced which, together with the relatively large size of helminth genomes, can still make whole-genome resequencing of individual parasites unfeasible for many studies. Fortunately, there are alternative approaches to the complete sequencing of genomes when conducting genome-wide studies. Here we review some strategies, including genome subsampling and pooling, that enable genome-wide analysis of large numbers of parasites in populations.