With wildfires increasing in activity in the Western United States and around the world, there is an immediate need to understand the toxic effects of the smoke. This chapter will provide a background of toxicology and apply principle concepts such as dose, duration and frequency to help define the potential effects of smoke exposure. Characteristics that influence toxicity will be discussed, which include particle size, source and temperature and the mixture of chemical constituents. An overview of the routes of exposure, mechanisms of action, toxicokinetics and the role of the immune system will all be covered. The importance and mutual benefits of in vitro, ex vivo and in vivo studies will be discussed. Finally, the chapter concludes by outlining knowledge gaps and research needs.