Introduction: This paper was written in response to a request from the U.S. National Cancer Institute. The goal is to discuss some research directions related to establishing tobacco product standards under the Family Smoking Prevention and Tobacco Control Act, which empowers the U.S. Food and Drug Administration to regulate tobacco products. Potential research related to tobacco product ingredients, nicotine, and harmful or potentially harmful constituents of tobacco products is discussed. Discussion: Ingredients, which are additives, require less attention than nicotine and harmful or potentially harmful constituents. With respect to nicotine, the threshold level in tobacco products below which dependent users will be able to freely stop using the product if they choose to do so is a very important question. Harmful and potentially harmful constituents include various toxicants and carcinogens. An updated list of 72 carcinogens in cigarette smoke is presented. A crucial question is the appropriate levels of toxicants and carcinogens in tobacco products. The use of carcinogen and toxicant biomarkers to determine these levels is discussed. Conclusions: The need to establish regulatory standards for added ingredients, nicotine, and other tobacco and tobacco smoke constituents leads to many interesting and potentially highly significant research questions, which urgently need to be addressed.