Diverticulosis of the colon is a common condition in western countries. Acute diverticulitis may occur in 10% to 25% of the patients, sometimes associated with the presence of complications such as abscess, fistula, and perforation. Early diagnosis and accurate assessment of acute diverticulitis are necessary to start an efficacious treatment promptly, either conservatively or by surgery. The clinical picture may mimic other abdominal conditions; therefore, imaging techniques such as ultrasound or computed tomography are usually recommended, although they are expensive, examiner dependent, and potentially harmful. Recently, there has been increasing interest about the role of biological markers in diverticular disease as noninvasive, reliable, and inexpensive tools, conceivably able to support physicians in the diagnosis, the assessment of activity, and the monitoring of acute diverticulitis. By a MEDLINE search, most of the relevant data derived from C-reactive protein showed that it strongly supported the diagnosis of acute diverticulitis at values of >50 mg/L. It also represents a stronger marker compared with other serum biomarkers, able to correlate with the histologic severity in acute diverticulitis, the risk of perforation, and the response to therapy. Regarding fecal biomarkers, an interesting role has been reported for fecal calprotectin. It significantly correlates with inflammatory infiltrate. More relevantly, it correlates with the response to therapy and may predict the recurrence of colonic diverticulitis, as it is reliable in detecting subclinical intestinal inflammation, as reported already for inflammatory bowel disease. These represent encouraging results, but need to be confirmed in further larger studies.