If the billions of oligodendrocytes (OLs) populating the central nervous system (CNS) of patients could express their feelings, they would undoubtedly tell gene therapists about their frustration with the other neural cell populations, neurons, microglia, or astrocytes, which have been the favorite targets of gene transfer experiments. This review questions why OLs have been left out of most gene therapy attempts. The first explanation is that the pathogenic role of OLs is still discussed in most CNS diseases. Another reason is that the so-called ubiquitous CAG, CBA, CBh, or CMV promoters-widely used in gene therapy studies-are unable or poorly able to activate the transcription of episomal transgene copies brought by adeno-associated virus (AAV) vectors in OLs. Accordingly, transgene expression in OLs has either not been found or not been evaluated in most gene therapy studies in rodents or non-human primates. The aims of the current review are to give OLs their rightful place among the neural cells that future gene therapy could target and to encourage researchers to test the effect of OL transduction in various CNS diseases.