RNA helicases of the DEAD-box family are found in all eukaryotes, most bacteria and many archaea. They play important roles in rearranging RNA-RNA and RNA-protein interactions. DEAD-box proteins are ATP-dependent RNA binding proteins and RNA-dependent ATPases. The first helicases of this large family of proteins were described in the 1980s. Since then our perception of these proteins has dramatically changed. From bona fide helicases, they became RNA binding proteins that separate duplex RNAs, in a local manner, by binding and bending the target RNA. In the present review we describe some of the experiments that were important milestones in the life of DEAD-box proteins since their birth 25 years ago.