Cardiovascular disease (CVD) begins early in the course of chronic kidney disease (CKD) and is the leading cause of death in patients with CKD. Preventing the development of CVD and establishing new clinical tools for identifying high-risk individuals, particularly those with an increased risk for cardiac death, is of clinical importance. Abnormality of heart rate variability (HRV) has been shown to be associated with CVD and CKD. Assessment of HRV is based on analysis of consecutive normal R-R intervals and may provide quantitative information on the modulation of cardiac vagal and sympathetic nerve input. In this brief manuscript, increased CVD risk among CKD patients, mechanisms due to autonomic nerves dysfunction, changes of HRV and potential measures to ameliorate clinical prognostic of CKD patients will be discussed.