Important findings over the last years have shed new light onto the mechanistic details of RNA degradation by members of the RNase II/RNB family of exoribonucleases. Members of this family have been shown to be involved in growth, normal chloroplast biogenesis, mitotic control and cancer. Recently, different publications have linked human orthologs (Dis3 and Dis3L2) to important human diseases. This article describes the structural and biochemical characteristics of members of this family of enzymes, and the physiological implications that relate them with disease. (C) 2013 John Wiley & Sons, Ltd.