We have initiated a project to sequence the genome of common milkweed (Asclepias syriaca, Apocynaceae). Milkweeds have served as a preeminent model system for the evolutionary ecology of plant reproduction, and have played important roles in studies of plant hybridization. They have also greatly contributed to the understanding of plant/herbivore co-evolution as mediated by host-plant chemistry, particularly in the case of the well-known interaction with the Monarch butterfly. Asclepias syriaca (native to the eastern United States, despite the name) is an appropriate target for genome sequencing, as it is the most heavily studied milkweed species in ecological and evolutionary studies. Our goal is to obtain ~60X coverage of the estimated 800 Mbp genome, relying on paired-end sequencing of libraries of different insert sizes and several mate-pair libraries. Substantial genomic data is available from two other members of Gentianales, Catharanthus (Apocynaceae) and Coffea (Rubiaceae), permitting the integration of de novo and reference guided assembly to generate contigs and a draft assembly. Automated annotation will be facilitated by the increasing availability of comparative data from Solanaceae, Gentianales and other Asterid genome projects. The draft assembly and annotations will be used to identify novel markers for use in the estimation of phylogenetic relationships among the ~115 species of Asclepias. The sequence data will also be made available as a community resource for studies of alkaloid biosynthesis, plant/herbivore coevolution and comparative genomics.