Biological control is increasingly used against invasive weeds of natural areas. Scientific and regulatory review of safety-related research occurs before candidate biological control agents can be released. To increase safety, efficacy, and transparency of the process, we suggest that, prior to establishing a project, a feasibility study be conducted on a potential target for biological control to judge whether the project is appropriate. The present paper is both a feasibility study of an important invasive weed and a guide to doing biological control feasibility studies on other weed pests. The invasive weed Dioscorea bulbifera L. threatens the biodiversity of many natural areas in the southeastern United States. Current control efforts directed against this invasive species include herbicidal or manual removal, both of which are costly and ineffective. Biological control using insects that selectively feed on this species while leaving desirable native and economic species unharmed may be a useful option. As herbivore host range may be limited by taxonomic affinities and the lack of sympatry with potential host species, we propose that this weed will be a relatively safe target because of taxonomic and geographic isolation from desirable native and economic plant species. The family Dioscoreaceae is poorly represented in North America, north of Mexico, and the two native species that are sympatric with the weed are from a different subgeneric taxon than the weed. The West Indian and northern Mexican species, while more diverse, are also assigned to different subgeneric taxa, and are geographically isolated from the northern range of the weed. Initial searches for biological control agents have begun and will continue within its large transcontinental native range. However, further research is needed that will better delimit the geographic origin of the weed's North American population within its large native range. This will aid in the detection of suitable natural enemies. Much of the information we acquired and analyzed in this feasibility study is required for the environmental assessment normally submitted for approval prior to the introduction of a biological control agent. We suggest that this type of analysis will be better considered at the beginning of the process. If this type of analysis is done prior to or at the beginning of projects, potential conflicts and risks can be judged and then better addressed during the projects to ultimately produce safer, more acceptable agents for biological control.