The limited efficacy of current therapeutic approaches for a number of socially relevant human diseases such as cancer and cardiovascular pathologies, has required the exploration of alternative and more effective therapeutic strategies. In the last two decades, nucleic acid based drugs have emerged as an attractive and novel alternative with great therapeutic potential. Among these molecules, hammerhead ribozymes were the first to be extensively studied and predicted to be of potential practical utility. Hammerhead ribozymes are catalytic RNA molecules capable of inducing the site-specific cleavage of a phosphodiester bond within an RNA molecule. Thus, they can be used to reduce the intracellular level of a specific mRNA coding for a protein which affects cellular metabolism or environment, causing disease. As hammerhead ribozymes can be engineered to reduce the level of virtually any mRNA, they have a very broad applicability. Among the several pathological conditions amenable for a hammerhead ribozyme based therapeutic approach, we focused our attention on pathologies sustained by a dis-regulated and excessive cellular proliferation, being sure to properly demonstrate their usefulness. Trying to be as objective as possible in regard to the feasibility of hammerhead ribozyme employment as therapeutics, a technical section, describing some of the unresolved problems in this field, has been also included. Although some aspects of hammerhead ribozymes as therapeutics can and should be optimized, the encouraging results displayed so far fully justifies further efforts, economic and scientific, to bring them closer to the clinical practice.