14-3-3 proteins regulate many cellular processes relevant to cancer biology, notably apoptosis, mitogenic signaling and cell-cycle checkpoints. Seven isoforms comprise this family of signaling intermediates, denoted 14-3-3 ?, ?, ?, ?, ?, ? and ?. 14-3-3 proteins form dimers that present two binding sites for ligand proteins, thereby bringing together two proteins that may not otherwise associate. These ligands largely share a 14-3-3 consensus binding motif and exhibit serine/threonine phosphorylation. 14-3-3 proteins function in broad regulation of these ligand proteins, by cytoplasmic sequestration, occupation of interaction domains and import/export sequences, prevention of degradation, activation/repression of enzymatic activity and facilitation of protein modification, and thus loss of expression contributes to a vast array of pathogenic cellular activities.