The Commerce Clause has been used by the federal government as a way to enact criminal laws on actions that have something to do with interstate commerce. There have been controversies as to how far Congress can extend this power.
For example, Congress used the Commerce Clause to justify a law that made it a federal crime to have a gun near a school. This was justified on the idea that the gun had been part of interstate commerce (it was made and sold in interstate commerce). This law was struck down in 1995.
Another example (that has not been struck down) is the Hobbs Act which makes robbery or extortion of anything involved in interstate commerce a federal crime. In this way, the Commerce Clause allows the Congress to make laws against robberies, even though those acts happen within a state.