There are three basic means of avoiding smoking-related diseases: never starting to smoke, quitting, and avoiding smoke-filled environments. Recently, a fourth possibility has emerged: use of new, ostensibly less toxic products by smokers who cannot or will not quit, including "reduced toxin" cigarettes and novel smokeless tobacco products. To their purveyors, these new "tobacco harm reduction" (THR) products represent an opportunity for inveterate smokers to reduce their risk of lung cancer and other diseases. To health professionals, the new products pose a myriad of risks. This new generation of THR products is not the first to promise reduced risk, however. Both filtered cigarettes and low tar and nicotine cigarettes were marketed with explicit health themes, ultimately with disastrous results for public health. THR products enter the market subject to no product regulation whatsoever; thus, the opportunity for objective, independent scientific evaluation of their risks and benefits, and for regulation of advertising or sale as a result, is absent. This paper describes the new generation of THR products, discusses potential benefits and risks, examines lessons from the experience with filtered and low tar and nicotine cigarettes, and describes the principal challenges that confront the medical profession, government, and the public in determining what to do with this perplexing array of novel products.