Smoking, leading to over 438,000 annual deaths in the US and 92 billion US dollars in lost productivity, is an important risk factor for several diseases. Global smoking statistics for 2002 have shown that 80,000 to 100,000 children worldwide start smoking every day. Human biomonitoring nowadays has provided an efficient and cost-effective means of measuring human exposures and biological effects of smoking. To review the utility of biomarkers in reflecting the hazard from cigarette smoking, we comprehensively searched the Cochrane Library, Medline and EMbase from 1966 to May 2010 with the language limit of English. We found that the currently used biomarkers, such as tobacco-specific metabolites, smoking-induced genotoxic products, may not scientifically reflect the hazard from cigarette smoking. More research is needed to find out more effective biomarkers for estimating hazards from cigarette smoking. This paper is expected to help researchers understand the current utilization of biomarkers related to cigarette smoking and to provide suggestive guides to tobacco companies in producing less-toxic cigarettes, thus to provide a safe way to smoke.