Many states are passing state sovereignty resolutions. Some, usually considered more "blue", are passing resolutions legalizing marijuana, usually for medicinal purposes but sometimes going as far as outright legalization. Others, usually considered more "red", are passing resolutions exempting citizens of that state from the insurance mandate included in the health care "reform" recently passed.
The problem is that at this point these resolutions are symbolic. While these resolutions will be challenged in federal courts (at which point the federal government will likely rule in its own favor) these resolutions lack any enforcement mechanism. The only resolutions that have any actual impact are the ones that prohibit a state from participating in REAL ID or PASS ID on the grounds that the state simply refuses to spend the money to comply with federal standards.
What, in any of these resolutions, will stop the DEA for the ATF from enforcing federal law on the citizens of states allegedly protected by these tenth amendment resolutions? Based on the continuing arrests of medicinal marijuana patients in California, apparently nothing. These resolutions lack an enforcement mechanism.
A better resolution would not only nullify the federal law in question - it would mandate that the state and local police not cooperate under any circumstances with the federal agency corresponding to the law in question, up to including punishments for police that do so. An even better resolution would mandate that the police arrest and the district attorneys file charges against federal agents for violating the rights of citizens of the state, and forbid transfer of these federal agents into federal custody.
It is absolutely certain that the federal government will attempt to challenge these laws. The question is how effective that would be. Any state legislature that has the courage to pass a nullification resolution with an enforcement mechanism would also have the courage to refuse to hand over any federal DEA or ATF agents. To get these agents would require an armed assault on the state prison system. To arrest politicians who stand up to the federal government would also require an armed assault. Will the federal government go that far?
This is not without precedent though. The State of Massachusetts nullified the Fugitive Slave Act before the civil war. The Fugitive Slave Act said that anyone who kidnaps a runaway slave is protected from prosecution but anyone who protects a runaway slave would be tried for violating the act. The nullification act passed by Massachusetts reversed the Fugitive Slave Act so that anyone who kidnapped a runaway slave would be tried and anyone who protected a runaway slave would be protected.
It is impossible, absent calling out the military, for the federal government to enforce laws that the state absolutely refuses to enforce. That's why nullification works, and why a nullification act with an enforcement mechanism is necessary.