Oplopanax horridus (OH) or Devil's club is an ethnobotanical used by the indigenous people native to the Pacific Northwest. There are three species in the genus Oplopanax, and OH is the only species that is distributed in North America. Compared with the extensive research on OH's “cousin,” American ginseng, there is comparatively little about the chemical makeup and pharmacological effects of OH. Nevertheless, there has been some research over the past few years that shows promise for future usage perspectives of OH. To date, seventeen compounds were isolated and elucidated including polyynes, glycosides, lignans, and polyenes, with most of the attention being paid to the polyynes. GC and HPLC were used to determine the contents of volatile compounds and polyynes in the essential oil and extracts of OH. For the pharmacological studies, antibacterial and anti-diabetes effects of polyynes were reported. Our recent study has focused more on the anticancer effects of OH and the involved mechanisms of action. In this review, we will summarize the research status in the botany, phytochemistry and pharmacology of OH.