"Today is a great day for America," President Joe Biden said during a Rose Garden address heralding the new guidance.
"If you are fully vaccinated, you no longer need to wear a mask," he said, summarizing the new guidance and encouraging more Americans to roll up their sleeves. "Get vaccinated - or wear a mask until you do."
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Pennsylvania has already made the decision to follow the CDC.
The guidance still calls for wearing masks in crowded indoor settings like buses, planes, hospitals, prisons and homeless shelters, but it will help clear the way for reopening workplaces, schools, and other venues - even removing the need for social distancing for those who are fully vaccinated.
The CDC says state, local and business rules must be observed.
Inside Gran Caffe L'Aquila in Philadelphia, it was business as usual. They haven't made any changes after the new guidelines.
"We don't ask people to wear masks because we want to be malicious or mean, but it's for their own safety and everyone around them because maybe not everyone in the restaurant at that time is vaccinated," said Darreno Jacobezzi, the general manager at Gran Caffe L'Aquila. "You have to assume they aren't until you know that they are."
Some Philadelphia residents say they are excited about the CDC's new guidelines, but the majority of people we spoke with say they still want to keep their mask on
"I'll still wear my mask because I still feel nervous about it," said Patrick Butler of Northeast Philadelphia.
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Others say they're concerned not everyone will be truthful about getting their shots.
"I think some people will lie about it, but the majority of people will tell the truth," said Loretta Carson of Boston, Massachusetts.
Cafe and restaurant employees we spoke with say they feel more safe wearing masks.
"I enjoy the mask, I think they do provide some protection," said Niyata Johnson, a barista at the Dilworth Park Café & Air Grille.