Regulators said it was the largest coordinated crackdown in the agency's history.
Under Wednesday's announcement, the five largest e-cigarette manufacturers will have 60 days to produce plans to reverse underage use of their products.
Shares of British American Tobacco, which owns the Vuse brand, closed up almost 6 percent, while shares of cigarette-maker Imperial Brands PLC, which owns Blu, rose more than 3 percent.
State health department officials continue to be anxious about JUUL, a device that looks like a flash drive, which they say dominates more than 70 percent of the e-cigarette market. The company has more than two-thirds of the USA e-cigarette market, according to Nielsen data.
The company has stressed that the device was created for adults who want to transition from regular cigarettes.
Gottlieb recently began to ask whether the use of Juul and other similar products by kids is overshadowing any benefit to adult smokers using the devices to help them quit cigarettes.
None of the other four companies contacted by the FDA immediately responded to TIME's requests for comment.
Many use fruit- or candy-flavored liquids that critics say appeal to kids, and risk addicting them to nicotine.
The FDA said Wednesday that it has issued more than 1,300 warning letters and fines to retailers that illegally sold e-cigarette products to minors during a national sting operation at brick-and-mortar and online stores this summer. In May, they were warned, but they are still advertising and selling the violative products.
"We're especially focused on the flavored e-cigarettes", said Gottlieb.
"I use the word epidemic with great care".
Budding research on e-cigarettes also suggests that these flavors contain terpenes that may be more damaging to the lungs than other flavors are.
Also, the agency is probing manufacturer's online shops for "straw" purchases in which buyers resell products to minors.
Since 2017, FDA officials have discussed e-cigarettes as a potential tool to ween adult smokers off cigarettes. "We can not allow a whole new generation to become addicted to nicotine".
FDA had taken a slow approach to allow manufacturers to figure out how to submit products for consideration.
"Far too many teens are being introduced at an early age to e-cigarettes", said Minnesota Education Commissioner Brenda Cassellius in the release. Ingredients also include glycerol, propylene glycol, natural oils, extracts and flavor and benzoic acid.
Juul Labs said it would work with the FDA and is committed to preventing underage use of its product.
In the US, about 12 percent of high school students use e-cigarettes at least once a month, the US Centers for Disease Control and Protection estimated in 2017. But spokeswoman Victoria Davis said "appropriate flavors play an important role in helping adult smokers switch". "By working together, we believe we can help adult smokers while preventing access to minors, and we will continue to engage with the FDA to fulfill our mission".
British American's R.J. Reynolds Vapor Company, said it will comply with the FDA request, adding that "youth tobacco prevention is a priority for our companies". "And we're seriously considering a policy change that would lead to the immediate removal of these flavored products from the market".
The FDA point out that, despite lacking tobacco and plenty of the nasties present in normal cigarettes, nicotine itself is hardly a benign substance.