According to the DSM-IV, Mental Retardation is significantly sub-average general intellectual functioning accompanied by significant limitations in adaptive functioning in at least two of the following skill areas: communication, self-care, home living, social/interpersonal skills, use of community resources, self-direction, functional academic skills, work, leisure, health and safety. In pilot work, we have seen positive clinical effects of Neurofeedback (NF) applied to children with Trisomy 21 (Down Syndrome) and other forms of mental retardation. Given that many clinicians use NF in Attention Deficit Hyperactivity Disorder and Generalized Learning Disability cases, we studied the outcomes of a clinical case series using Quantitative EEG (QEEG) guided NF in the treatment of mental retardation. All 23 subjects received NF training. The QEEG data for most subjects had increased theta, alpha, and coherence abnormalities. A few showed increased delta over the cortex. Some of the subjects were very poor in reading and some had illegible handwriting, and most subjects had academic failures, impulsive behavior, and very poor attention, concentration, memory problems, and social skills. This case series shows the impact of QEEG-guided NF training on these clients' clinical outcomes. Fourteen out of 23 subjects formerly took medications without any improvement. Twenty-three subjects ranging from 7-16 years old attending private learning centers were previously diagnosed with mental retardation (severity of degree: from moderate to mild) at various university hospitals. Evaluation measures included QEEG analysis, WISC-R (Wechsler Intelligence Scale for Children-Revised) IQ test, TOVA (Test of Variables of Attention) test, and DPC-P (Developmental Behaviour Checklist) were filled out by the parents. NF trainings were performed by Lexicor Biolex software. NX-Link was the commercial software reference database used to target the treatment protocols, along with the clinical judgment of the first author. QEEG signals were sampled at 128 samples per second per channel and electrodes were placed according to the International 10-20 system. Between 80 and 160 NF training sessions were completed, depending on the case. None of the subjects received any special education during NF treatment. Two subjects with the etiology of epilepsy were taking medication, and the other 21 subjects were medication-free at the baseline. Twenty-two out of 23 patients who received NF training showed clinical improvement according to the DPC-P with QEEG reports. Nineteen out of 23 patients showed significant improvement on the WISC-R, and the TOVA. For the WISC-R test, 2 showed decline on total IQ due to the decline on some of the subtests, 2 showed no improvement on total IQ although improvement was seen on some of the subtests, however even these cases showed improvement on QEEG and DPC-P. This study provides the first evidence for positive effects of NF treatment in mental retardation. The results of this study encourage further research.