Nullification is the act of states refusing, or nullifying, laws imposed by the federal government that the states consider to be unconstitutional. The supposition is that nullification is itself unconstitutional, but upon further investigation, it might not be so.
First of all, the Constitution is essentially a contract between the states and the federal government. The contract called for each of the states to cede some aspects of self-government to the federal government so that the federal government could act for the general good of all of the states. One of the powers the states granted to the federal government was the ability to collect taxes, duties and imposts in order to provide for the common defense. The "common defense" was meant to give all of the states a stake in the attack on any individual state.
This very simple understanding has fallen from common discussions on the issue, because the federal government has gone outside of its mandate. It is difficult now to look at some of the things the federal government has done, such as Social Security, and see it for what is: an abuse of power. The mind asks the obvious question of "who else could do it?" The mind is not trained to ask the more appropriate question of "why couldn't the states do it for themselves?"
All that has been done by looking to the federal government to satisfy some social desire is to give power where it does not belong and is harder to revoke. Where the people of one state might find Social Security to be a financial disaster, it is unable to extricate itself from the federal obligation. If Social Security, or something like it, were a state program it would be much easier for the people to determine the future of the program as the state would owe its fealty to no other.
The best Constitutional argument for Nullification can be found at Publius Huldah's blog.
I won't go into it better than that, so go there and read for yourself. The point is that if we are to return to a Constitutional Republic, which we have not been for a long time, it will take some serious readjustments to our ways of thinking. We have got to stop relying on the federal government to provide for us if we expect to be able to control the budgets and destinies of our states. Perhaps the upcoming civil unrest will give us the opportunity to put federalism back into the box, but it will not be possible if the Constitutionally-motivated people remain distant and apart from each other; if Threepers refuse to engage and cooperate with Tea Parties and 912's; if the conservative cross-section does not embrace each aspect the statists will quickly and permanently draw power to itself and re-write the Constitution to give all power to the federal government and the very concept of limitation will be lost forever. Liberty will be a slogan used by statists to justify collectivism.
Tom Woods speech on Nullification.