The genus Mycoplasma comprises various species that live as commensals or pathogens on the mucous membranes of humans and animals. Unlike other prokaryotes, these bacteria lack the cell wall, making them intrinsically resistant to antibiotics that inhibit peptidoglycan synthesis. Clinically significant representatives include Mycoplasma pneumoniae, Mycoplasma genitalium, and Mycoplasma hominis. M. genitalium is an emerging pathogen and a known cause of sexually transmitted infections. Due to its reduced genome and significant metabolic restrictions, it directly depends on the host for its survival, but cultivating this bacterium is extremely challenging. Several virulence factors enable it to adapt to a parasitic way of life, with the terminal organelle being the most important among them. As a sexually transmitted infection, M. genitalium spreads through direct contact between the infected mucous membranes. Increased infection rates are found in certain high-risk groups, while the prevalence in the general population is low. The most common syndromes caused by this mycoplasma are non-gonococcal urethritis, cervicitis, and pelvic inflammatory disease, whereas persistent infection can lead to infertility in both sexes. Molecular diagnostic methods revolutionized the detection of this bacterium, which was previously exceedingly challenging. A single dose of azithromycin used as a syndromic treatment has led to the selection and rapid spread of macrolide-resistant strains, particularly among the high-risk populations, consequently increasing the use of moxifloxacin. However, the emergence of fluoroquinolone resistance genes has been recognised, and combined resistance to both antibiotics is being reported as well. Therefore, existing therapeutic options should be reevaluated and regular surveillance of resistant strains in the population should be implemented. Ultimately, this bacterium should be included in the diagnostic protocol for the management of common infections, along with the introduction of mandatory test of cure to assess treatment success to curb further spread of resistance.