Prostitute women have the highest homicide victimization rate of any set of women ever studied. We analyzed nine diverse homicide data sets to examine the extent, trends, and perpetrators of prostitution-related homicide in the United States. Most data sources substantially under-ascertained prostitute homicides. As estimated from a conservative capture-recapture analysis, 2.7% of female homicide victims in the United States between 1982 and 2000 were prostitutes. Frequencies of recorded prostitute and client homicides increased substantially in the late 1980s and early 1990s; nearly all of the few observed pimp homicides occurred before the late 1980s. These trends may be linked to the rise of crack cocaine use. Prostitutes were killed primarily by clients, clients were killed mainly by prostitutes, and pimps were killed predominantly by pimps. Another conservative estimate suggests that serial killers accounted for 35% of prostitute homicides. Proactive surveillance of, and evidence collection from, clients and prostitutes might enhance the investigation of prostitution-related homicide.