During the last 20 years or so, there have been many issues regarding federalism and the scope of the Commerce Clause. The general conflict here has been over how far the federal government may go in regulating activity that occurs within a state while justifying those regulations through the Commerce Clause.
One example of this was the case of United States v. Lopez, decided in 1995. There, the Court invalidated a federal law that banned people from knowingly possessing guns in a school zone. The Court ruled that the act of possessing a gun in such a place was not sufficiently connected to interstate commerce. Therefore, the law was unconstitutional.
Ten years later, in Gonzalez v. Raich the Court came to the opposite conclusion with regard to medical marijuana. In that case, the Court ruled that marijuana grown for personal medical use was still part of interstate commerce. This allowed the federal government to override state laws allowing medical marijuana.
Today, the fight over "Obamacare" hinges in part on the Commerce Clause. The Court will have to decide whether the Commerce Clause allows the federal government to require people in the states to buy health insurance.
These three instances show that the interpretation of the Commerce Clause has a great deal to do with recent conflicts between the states and the federal government.