My major brick wall breakthroughs were both accomplished with the help of DNA. We had names for both of my mother's grandfathers, and for one we had a 1900 census record, but both men disappeared.
For the Norwegian immigrant (he of the 1900 census and a marriage record), there were several candidates with the right name and approximate age. DNA proved that he was the candidate who came from the same community as my great-grandmother but immigrated with his first wife, who divorced him (as did my great-grandmother, his second wife, after he disappeared). We'd now like to find out where he went.
For the other, who was briefly around in 1890, we had a name in the family Bible, which later proved to be close but not quite correct (Allen Morey for Albert Mory). For a while, it looked like we had nailed it down to a married Allen Morey living not impossibly farther west, but DNA was not providing any links to him (or, to the best of our knowledge, to anyone else). After some years, Albert's relatives began to do a little DNA testing, and we were eventually able to determine that he was the son of German immigrants, which explained why my mother had one fairly close German DNA match (previously assumed to be on her Norwegian side). Through his family, we learned that he moved to Texas and changed his name to Fuller.
The next brick wall we hope to solve through DNA would be the parentage of my Huebner g-g-grandfather, who first appears in the records already married and baptizing his children. It'd be nice if more Huebner men did Y tests (it's a common surname and they're not all related). So far we just have my brother and an out-of-wedlock cousin matching on Y.