Novel tobacco products, such as little cigars, cigarillos, hookah, and e-cigarettes, and their smoke or aerosol contain chemicals which the FDA has determined to be Harmful or Potentially Harmful Constituents. We explored adolescents' and young adults' knowledge and beliefs about constituents in novel tobacco products and their smoke or aerosol, in order to inform risk communication messages. Seventy-seven adolescents and young adults (ages 13-25) participated in 10 focus groups, including 47 novel tobacco product users and 30 susceptible nonusers. Participants were asked to discuss 10 pre-selected constituents found in novel tobacco products and their smoke or aerosol. The first author analyzed the discussion for emergent themes. Participants were generally familiar with arsenic, carbon monoxide, formaldehyde, and nicotine, but unfamiliar with acetaldehyde, acrolein, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanon (NNK), and N-nitrosonornicotine (NNN). All participants had negative beliefs about most constituents, although users had positive beliefs about nicotine. "Unfamiliar" constituents were associated with similarly-sounding words (eg, acetaldehyde sounds like acetaminophen), and some participants recognized words in the chemical names of NNK/NNN (eg, "nitro"). "Familiar" constituents were associated with negative health effects and other common products the constituents are found in. All participants wanted more information about the constituents' health effects, toxicity, and other common products. Most participants were unaware the constituents discussed are in novel tobacco products and their smoke or aerosol. Risk communication messages could capitalize on negative associations with familiar constituents, or attempt to educate about unfamiliar constituents, to discourage novel tobacco product use among adolescents and young adults. The results of this study have implications for how the FDA and other agencies can communicate about the risks of novel tobacco products to the general public, which will be particularly important once the Deeming Rule is finalized. Our findings suggest it may be effective to capitalize on the public's negative beliefs about and associations with familiar constituents, or to educate about unfamiliar constituents and their health effects, their concentration and toxicity in novel tobacco products and their smoke or aerosol, and other products they are found in.