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Despite the success of neurofeedback treatment in many cases, the variability in the efficacy of the treatment is high, and some studies report that a significant proportion of subjects does not benefit from it. Quantifying the extent of this problem is difficult, as many studies do not report the variability among subjects. Nonetheless, the ability to identify in advance those subjects who are – or who are not – likely to benefit from neurofeedback is an important issue, which is only now starting to gain attention. Here, we review the problem of inefficacy in neurofeedback treatment as well as possible psychological and neurophysiological predictors for successful treatment. A possible explanation for treatment ineffectiveness lies in the necessity to adapt the treatment protocol to the individual subject. We therefore discuss the use of personalized neurofeedback protocols as a potential way to reduce the inefficacy problem.