TNF inhibitors, even though being a powerful therapeutic tool, have their serious adverse effects, among which those involving the nervous system have raised a serious concern. A great debate about a possible causality link between TNF-antagonists and demyelinating diseases is still ongoing. This article attempts to critically review available data, starting from data on the biology of TNF and (de)myelination, and taking a closer look on two large studies, a systematic review and a smaller well-designed prospective study.