The regulation of protein synthesis plays as important a role as transcriptional control in the control of gene expression. Once thought solely to act globally, translational control has now been shown to be able to control the expression of most genes specifically. Dysregulation of this process is associated with a range of pathological conditions, notably cancer and several neurological disorders, and can occur in many ways. These include alterations in the expression of canonical initiation factors, mutations in regulatory mRNA sequence elements in 5' and 3' untranslated regions (UTRs), such as upstream open reading frames (uORFs), internal ribosome entry segments (IRESs) and micro-RNA (miR) target sites, and the altered expression of trans-acting protein factors that bind to and regulate these elements. Translational control is increasingly open for study in both fresh and fixed tissue, and this rapidly developing field is yielding useful diagnostic and prognostic tools that will hopefully provide new targets for effective treatments.