Despite medical cannabis laws in 46 states, cannabis is still illegal under federal law. The federal government regulates drugs through the Controlled Substances Act (CSA) (21 U.S.C. § 811), which does not recognize the difference between medical and recreational use of cannabis. These laws are generally applied only against persons who possess, cultivate, or distribute large quantities of cannabis.

There are two types of federal sentencing laws: sentencing guidelines, enacted by the United States Sentencing Commission, and mandatory sentencing laws, enacted by Congress. The Sentencing Commission was created in 1987 to combat sentencing disparities across jurisdictions. The current mandatory minimum sentences were enacted in a 1986 drug bill. Federal sentencing guidelines take into account not only the amount of cannabis involved in the arrest but also the past convictions of the accused. Not all cannabis convictions require jail time under federal sentencing guidelines, but all are eligible for imprisonment.

In United States v. Booker (2005), a Supreme Court decision from January 2005, the court ruled that the federal sentencing guidelines (as outlined above) are advisory and no longer mandatory.