Destructive periodontal disease has been primarily defined and investigated as an infectious disease. The aim of this study was to systematically search for cohort studies where microbiological diagnoses were performed before the onset of destructive periodontal disease and where statistically significant associations were identified. A search was executed in PubMed. The results showed that three studies published after 2005 supported the infection hypothesis for one putative periodontal pathogen: Aggregatibacter actinomycetemcomitans. These three studies were conducted in predominantly non-Caucasian pediatric populations living in geographic areas with an elevated child-mortality rate. These studies did not obtain physical or laboratory markers of health, making it possible that A. actinomycetemcomitans was not a cause but a marker for poor environmental or systemic health. No cohort studies were identified supporting the infection hypothesis in adults, Caucasians or in a population residing in areas with child-mortality rates reflective of healthy population goals. While the possibility cannot be excluded that A. actinomycetemcomitans has an etiological role in certain specific pediatric populations, there are no cohort studies supporting an infectious etiology of destructive periodontal disease in adults.