Recent studies have demonstrated the potential of DNAzymes for therapy of various diseases via mRNA target-specific cleavage. One such target, the basic region-leucine zipper protein c-Jun, has been targeted and efficacy seen in such pathologies as cancer, ocular neovascularisation, arterial thickening, acute inflammation, and rheumatoid arthritis. This review discusses these cases in turn, and presents some new data on the applicability of a c-jun DNAzyme against a panel of cancer cells. Importantly, downregulation of c-jun is noted to cause apoptotic death of cancer cells. These studies collectively demonstrate the potential of this DNAzyme as a lead candidate for DNAzyme therapeutics.