There is an ongoing debate about the 'usefulness' of the standard machine smoking regimen for cigarettes defined by the US Federal Trade Commission (FTC) and adopted in principal by the International Organization for Standardization (ISO). More intense smoking regimens result in much higher smoke yields, and these higher yields have been suggested to be much closer to human smoke uptake. However, it appears that more intense smoking regimens are less efficient in detecting possible differences in the yield of toxicants. Intense smoking regimens reproducibly decrease the concentration of toxicants in the smoke per unit mass of total particulate matter, tar, or nicotine, most likely as a result of a more complete combustion. The toxicant concentration reaches the same plateau for different cigarette types under the intense smoking regimens. As such, differences in toxicant concentrations due to product changes, which are observable under ISO or FTC conditions, may disappear under intensive smoking regimens. Intense machine smoking regimens might be used for regulatory compliance and consumer information. However, when evaluating the toxicological impact of cigarette product changes, especially to avoid increases in toxicity, they should not be used as a standard (or at least not as the only standard). The type of smoking regimen has to be carefully considered and aligned to the underlying question. Depending on the question a combination of the reviewed regimens or even other approaches might be appropriate.