Streptomyces is the most important bacterial genus known to produce secondary antibiotic compounds. Considering the speed of bacterial resistance spread, it becomes more important to study less used compounds. Aminoglycosides disrupt the function of the target microorganism by acting on the protein-synthesis process. Paromomycin is an aminoglycoside that acts on a wide range of gram-positive, gram-negative bacteria and protozoa. Today, this antibiotic is mostly used in the treatment of visceral leishmaniasis. The main producer of paromomycin is S. rimosus NRRL 2455. Taking these antibiotics in high doses can cause widespread complications in the heart, kidneys, and auditory system, but in low doses and in combination with other types of antibiotics, it can significantly inhibit the growth of multidrug-resistant (MDR) bacteria. According to this information, it is important to know the factors that increase production and to understand the relationship between the structure and performance of this antibiotic. The aim of this study was to collect useful and up-to-date information about paromomycin, production conditions and the importance of this antibiotic in the treatment of bacterial MDR infections.