All fifty states and the federal government have passed laws to combat human trafficking, but we know little about their effectiveness. Using data from investigative case records and court files for 140 human trafficking cases in 12 U.S. counties and qualitative interviews with law enforcement, prosecutors, and victim service providers, we examined the characteristics of and challenges to investigation and prosecution of human trafficking cases under new state and federal laws. We found that few human trafficking cases are identified by local law enforcement, most cases forwarded to state prosecution are sex trafficking cases involving U.S. citizens, and state prosecutors overwhelmingly charge human trafficking offenders with other, lesser crimes. The legal, institutional, and attitudinal challenges that constrain prosecution of human trafficking are similar across study sites despite varying types of state antitrafficking legislation. Study results suggest prosecution of human trafficking cases is challenging. If new laws are to be effective, then local law enforcement and prosecutors should work collaboratively and adopt proactive human trafficking investigative strategies to identify both labor and sex trafficking cases. There is social benefit to holding traffickers accountable, but more emphasis should be placed on policies that identify and serve victims.