Anastomotic leakage is the most common major complication after mid-low rectal cancer surgery. Due to lack of knowledge regarding the virtual mechanisms of anastomotic leakage, not much can be done to prevent its development. The aim of the present review was to discuss the prevention, early diagnosis, and treatment of anastomotic leakage after rectal cancer surgery. For patients with risk factors, such as anastomotic site within 4 cm from anus, obese men, lack of blood supply of the anastomotic site, neoadjuvant chemo radiotherapy, or patients with severe co-morbidity, aggressive preventive strategy should be adopted. The effectiveness of diverting stoma, preoperative bowel preparation, and transanal decompression are still in debate. The combination of fluorescence imaging to assess anastomotic perfusion and selective preservation of the left colic artery can be used in the future to prevent anastomotic leakage intraoperatively. With increasing use of neoadjuvant chemo radiotherapy and diverting stoma, more than half of the leaks present in a more subtle and insidious manner, including ileus, diarrhea, anal discharge of pus, mild fever, accelerated heart rate, tachypnea, and oliguria. Surgeons should be more cautious regarding these insidious clinical presentations. Computed tomography scan and endoscopy are among the most important diagnostic workups that can early diagnose leakage and indicate the size of the defect and extent of infection. For patients presenting with diffuse peritonitis, emergency surgical exploration is mandatory along with fluid resuscitation. For those with limited infection, appropriate treatment plan should be made after consideration of the extent of infection, methods to eradicate the infectious source, strategies following adjuvant therapy, and the possibility and necessity of re-establishing bowel continuity.