The book is set in the town of Hemlock Grove, Pennsylvania. The town is a mixture of extreme wealth and poverty, as the closing of the town's steel mill (owned by the Godfrey family) many years earlier cost a lot of people their jobs. Now the town's main sources of employment are the Hemlock Acres Hospital and the Godfrey Institute for Biomedical Technologies. Run by the powerful Godfrey family, the Institute is rumored to have several sinister experiments take place within. The town's rumor mill turns even more twisted when a teenage girl is brutally killed during a full moon. Peter Rumancek, a 17-year-old Romani who just moved to Hemlock Grove with his mother, is suspected of the crimes by some of the townsfolk and is also rumored to be a werewolf. While he secretly really is a werewolf, he isn't the actual killer and along with Roman, the heir to the Godfrey estate (who Peter realizes is an upir, though Roman does not know it himself), they set out to find the killer.