Nematodes are very common animals and they have repeatedly evolved parasitic lifestyles during their evolutionary history. Recently, the genomes of many nematodes, especially parasitic species, have been determined, potentially giving an insight into the genetic and genomic basis of nematodes' parasitism. But, to achieve this, phylogenetically appropriate comparisons of genomes of free-living and parasitic species are needed. Achieving this has often been hampered by the relative lack of information about key free-living species. While such comparative approaches will eventually succeed, I suggest that a synthetic biology approach – moving free-living nematodes towards a parasitic lifestyle – will be our ultimate test of truly understanding the genetic and genomic basis of nematode parasitism.