Sphingolipids (SLs) are fundamental components of eukaryotic cells. 1-Deoxysphingolipids differ structurally from canonical SLs as they lack the essential C1-OH group. Consequently, 1-deoxysphingolipids cannot be converted to complex sphingolipids and are not degraded over the canonical catabolic pathways. Pathologically elevated 1-deoxySLs are involved in several disease conditions. Within this review, we will provide an up-to-date overview on the metabolic, physiological and pathophysiological aspects of this enigmatic class of “headless” sphingolipids.