I focus my practice on tax resolution, representing taxpayers in Colorado, Florida, Texas, New York, California and elsewhere. The single biggest thing you can (and NEED) to do is get into compliance (ie - file your tax returns). The IRS simply will not deal with you or speak to you unless they have the returns to work off of.
Ideally, no matter what your tax filing situation is, the ultimate goal is pretty straight forward: file all of your back returns (typically the six most recent prior years), and deal with whatever amounts you owe for those years. There are several collection alternatives to resolve your situation such as an installment agreement and non collectible status.
Equally important is getting up to date with your current year taxes. Just because your prior years have been dealt with doesn't mean you're done; the IRS wants to see you be in compliance for the current and future years. This means having sufficient withholding from your paycheck if you're an employee, or making sufficient estimated tax payments on a quarterly basis throughout the year. Taking this action will also greatly reduce and/or eliminate penalties and interest. Wouldn't you rather have that money in your pocket to spend the way you wish instead of paying the IRS unwanted penalties and interest, year after year?
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Boulder, CO 80305