Tobacco and tobacco smoke are both complex mixtures. We previously reported 8430 unique chemical components identified in these complex mixtures but two years later our updated number is 8877. Our previous number of 4992 identified tobacco components is now 5204; our previous number of 5311 identified tobacco smoke components is now 5679. An operational definition of a complex mixture is as follows: A complex mixture is a characterizable substance containing many chemical components (perhaps thousands) in inexact proportions. Detailed knowledge of the amount and type of each component within the substance is uncertain even with today's analytical technology. Although it has been estimated that as many as 100000 components are present in these complex mixtures, their analyses of indicate that the vast majority of the mass of each of these complex mixtures accounts for the 8430 compounds reported previously. Over 98.7% of the mass of tobacco has been accounted for in terms of identified components in tobacco. Greater than 99% of the mass of whole smoke has been accounted for based on identified chemical components. Certainly, many more tobacco and tobacco smoke components are present in these complex mixtures but the total mass of these components obviously is quite small. One of the significant challenges we face as a scientific community is addressing the problems of determining the risk potential of complex mixtures. Many issues are associated with toxicological testing of the complex mixture of tobacco smoke. Conducting valid experiments and interpreting the results of those experiments can be quite difficult. Not only is the test agent a complex mixture but also the tests are performed on species that have complicated life-processes. Interpretations of test results are often paradoxical. Significant progress has been made in the toxicological evaluations of complex mixtures in the last 80 years. The challenges we face in terms of testing the biological properties of tobacco smoke are substantial. The statement by DIPPLE et al. in their summary of the research on polycyclic aromatic hydrocarbons from the 1930s through 1980 is equally true today for the cigarette smoke situation: ¼many important questions remain unanswered…many questions persist despite the considerable progress that has been made.