Ribozymes, also known as RNA enzymes, are catalytic RNA molecules capable of cleaving specific RNA sequences, leading to decreased expression of targeted genes. Recent studies suggest their role in cancer therapeutics, genetic diseases and retroviral infections. This book chapter will focus on ribozymes acting as therapeutic agents against infectious diseases caused by viral and bacterial pathogens. Firstly, we will introduce a brief history of ribozymes and a general overview of ribozymes and their characteristics. Next, different types of ribozymes will be explored regarding their targets and mechanisms of action. After that, ribozymes specific to viral and bacterial infections will be explored. We will briefly discuss the current status of ribozymes as therapeutic agents. Finally, the roadblock and challenges ribozymes face before being developed into therapeutic agents—such as their delivery and efficacy issues—will be discussed.