Horseweed (Conyza canadensis) was the first broadleaf weed to evolve glyphosate resistance 10 years ago in Delaware and now is the most widely distributed glyphosate-resistant weed in the USA and the world. In the past decade, there has been a tremendous increase in the genomic tools for key crop plants and widely-used model systems, while, genomic research toward to understand the biological mechanism of significant traits in those economic important weedy plants remains scant. Horseweed is a true dicot (2n=2x=18) with the smallest genome of any agricultural weed (335 Mb) and was suggested among the best candidates of model weedy plant. Fifty-seven horseweed populations (>1400 individual plants) were collected from 11 US states and Saskatoon in Canada. Phenotypes of these populations were tested with herbicide sprayed experiments. Microsatellite makers were screened and used for genotyping of these populations. Next-generation sequencing of the horseweed shoot transcriptome has provided some of the first genomic data of any weeds. The results suggested that ATP-binding cassette (ABC) transporter genes play a role in glyphosate resistance in horseweed. Candidate ABC transporter genes are being cloned for use in gene overexpression and knock-down functional analysis. Deep-transcriptome sequencing of both glyphosate resistant and susceptible biotypes will be used for comparative analysis to obtain more targets. The complete horseweed genome is also being sequenced as a weedy model. Two plates of 454 Titanium runs generated 0.9 Gb data, including a complete sequencing of the chloroplast genome and almost all of the mitochondrion genome, repeats and transposable elements were analyzed. These data provided much of the scaffold, which will be used to enable the assembly short reads provided by subsequent sequence from the Illumina HiSeq. The information collected from this study should be beneficial not only for improved weed management of this resistant biotype, but also to increase the understanding of weed biology.