Periodontitis is a chronic inflammatory disease of the tooth-supporting connective tissue and alveolar bone that is initiated by a bacterial biofilm in periodontal pockets. It affects about half of adults in the Western world, and is associated with a range of systemic comorbidities, e.g., cardiovascular disease (CVD), diabetes and rheumatoid arthritis, and these diseases share overlapping systemic and target tissue inflammatory mechanisms. Indeed, mounting evidence has indicated that their association is causal and built on the presence of systemic low-grade inflammation (LGI). Prior research linking periodontitis to CVD has mainly been derived from experimental studies, observational data, and small interventional trials with surrogate markers of CVD, e.g., endothelial dysfunction. However, recent data from randomised studies have demonstrated that intensive treatment of periodontitis can reduce blood pressure in patients with hypertension in conjunction with reduction of systemic inflammatory markers. Furthermore, targeted anti-inflammatory therapy has been shown to reduce recurrent events in patients with established CVD and LGI. Along this line, the concept of residual inflammatory risk has emerged as an independent new risk factor for atherothrombotic CVD. The present review summarizes translational evidence indicating that periodontitis is a risk factor for CVD dependent on LGI, and we conclude that treatment of periodontitis is likely to contribute importantly to reduction of residual inflammatory risk.