Cognitive Remediation Therapy (CRT) deals with the cognitive impairment, which is one of the most disabling symptoms of schizophrenia. Unfortunately, the understanding of its neurobiological correlates is far from complete. Neuroimaging studies have shown that CRT is able to induce neurobiological changes although the results have not always been enough replicated. The most commonly reported changes were those that involved the prefrontal and thalamic regions. Additionally, structural changes were described in both the grey and white matter, suggesting a neuroprotective effect of cognitive remediation. Neuroimaging studies of cognitive remediation in patients with schizophrenia suggest a positive effect on brain functioning in terms of the functional reorganisation of neural networks. From a different perspective, some changes in serum levels of Brain derived neurotrophic factor (BDNF) have been described. However, our replication of this trial has not been able to find any significant differences. So, nowadays the status of BDNF as a biomarker of cognitive recovery is possibly premature. One possible explanation can be the role of genetics and their different polymorphisms. COMT and BDNF polymorphisms could be accounting for the different outcomes of CRT. Moreover, some studies suggested a role of genes affecting dopamine modulation on outcomes of cognitive remediation.