Combined use of niacin with a statin is an attractive option, since these types of medication have the best records in clinical trials for reduction in cardiovascular events and improvement in progression/regression of coronary lesions. In early use, the niacin–statin combination generated a few case reports documenting severe myopathy and rhabdomyolysis. Subsequent prospective trials in >400 patients, however, have not encountered myopathy. This experience includes 165 patients who took a statin in combination with Niaspan, a new, extended-release niacin administered once nightly. Hepatic toxicity with immediate-release niacin and with Niaspan used in combination with statins has been minimal. However, substantial transaminase elevations occurred with the use of a sustained-release niacin (Nicobid) given twice daily. The niacin–statin treatment regimens gave augmented low-density lipoprotein (LDL)-cholesterol reduction along with favorable changes in high-density lipoprotein (HDL) cholesterol, lipoprotein(a), and triglycerides. This combination therapy can be used safely as long as (1) careful attention is given to niacin formulation and dosing; (2) liver functions are monitored; and (3) patients are educated to recognize symptoms of myopathy. However, special caution should apply to use of niacin in combination with high doses of statins, or with statins introduced into clinical practice in 1997 or later, since little experience has accumulated in these circumstances.