Infectious diseases are among the main causes of morbidity and mortality today. In facing this crisis, the development of new drug options and combat strategies is necessary. In this sense, drug repositioning or drug redirection has emerged for the faster identification of effective drugs. In this "Commentary," the anti-infective properties of the class of proton pump inhibitors (PPIs) are emphasized. Studies report activities against bacterial, fungal, parasitic, and viral agents. In addition, we have provided in a table a summary of the specific characteristics of PPIs and some of their anti-infective activities.