This literature review summarizes current knowledge on the systemic levels of selected markers of inflammation in periodontitis. From samples of peripheral blood the following cellular factors are discussed: total number of white blood cells, red blood cells, and thrombocytes. Further, plasma levels of acute-phase proteins, cytokines, and coagulation factors are reviewed. From the available literature it appears that the total numbers of leukocytes and plasma levels of C-reactive protein are consistently higher in periodontitis patients compared to healthy controls. Numbers of red blood cells and levels of hemoglobin are lower in periodontitis and there is a trend towards anemia of chronic disease. Most systemic markers of inflammation discussed in this review are also regarded as predictive markers for cardiovascular diseases. Therefore, changes in these markers in periodontitis may be part of the explanation why periodontitis is associated with cardiovascular diseases and/or cerebrovascular events in epidemiological studies. It is hypothesized that possibly daily episodes of a bacteremia originating from periodontal lesions are the cause for the changes in systemic markers in periodontitis; the cumulative size of all periodontal lesions in the untreated severe patient may amount to 15 to 20 cm2.