Identification of the cause of the development and progression of periodontitis has received extensive attention, with notable advances over the past decade in clinical, microbiological, immunological, biochemical, and behavioral knowledge. However, it is still largely unknown which factors lead to the conversion of non-destructive forms of periodontal disease into destructive forms and disease progression. Chronic adult periodontitis is believed to be influenced by an interaction of host defense and environmental factors. Although these variables have been studied extensively, no study has employed randomized controlled prospective human or randomized controlled community intervention designs, methodologies necessary to prove a variable to be a cause of periodontitis. Owing to the absence of literature employing rigorous experimental design, this article assesses systematically observational, cross-sectional and longitudinal studies to examine the potential causal association between cigarette smoking and periodontitis. The methodology of Sir Bradford Hill's criteria for causation was used as the framework. Results suggest that cigarette smoking is causally associated with periodontitis. That is, cigarette smoking is consistently associated with an increased prevalence/severity of periodontitis and is suspected on theoretical grounds of playing a causal role. Hill's criteria provide a useful methodology to better understand the pathogenesis of periodontal diseases and may be applied to study the pathogenesis of other dental diseases as well.