However, a new study says that's not always the case.
A team at the Cleveland Clinic has discovered that when HDL is floating through our bloodstream, it does a lot of good.
But when it latches to the artery wall, a protein which gives HDL its heart-protective effect changes.
Then, this molecular Dr. Jekyll turns into Mr. Hyde, actually contributing to the development of heart disease.
Dr. Stanley Hazen, who led the research, says, "It's a big advance in terms of first, being able to identify people who are at risk, who we didn't understand were at risk."
Doctors have always wondered why so many people with good cholesterol profiles - including high levels of HDL - would still have heart attacks.
"The discovery is also a way of monitoring the HDL-raising efforts by so many drug companies that have been failing," Dr. Hazen continued.
For years, doctors have been stumped on why experimental drugs could raise the HDL, but fail to decrease heart disease.
Now they know it was because what was happening in the bloodstream didn't always reflect what was happening on the artery wall.