Difficulties in prescribing antibiotics for lower urinary tract infections (UTI) are associated with a fact that such patients can be treated not only by urologists, but also by general practitioners, internists, pediatricians, and gynecologists. Therefore, it is important to adapt the practical recommendations for the treatment of cystitis for different medical disciplines. When creating clinical guidelines, experts take into account the different factors in choosing antibiotic therapy. First of all, pharmacokinetics is of importance and drugs with renal excretion should be preferred. Secondly, the natural activity of the antibiotic against the pathogens, which cause cystitis, has to be considered. In uncomplicated infections, E. coli predominates, while in complicated and recurrent infections E. coli and other enterobacteria are commonly isolated, as well as Enterococci. In addition, local resistance pattern is reviewed. In the Russian Federation E. coli has minimal resistance to nitrofurans and fosfomycin. Lastly, antibiotics can negatively affect the gastrointestinal and urinary tract microbiota and contribute to the increase of antibiotic resistance and the selection of antibiotic-resistant strains, therefore the environmental safety of therapy should be considered. The effect of antibiotics on the resident flora of the gastrointestinal tract, urinary tract and vagina is called collateral effect, or concomitant (parallel) damage, and it may exceed the therapeutic effect of some antibiotics. Cephalosporins and fluoroquinolones can cause ecologically unfavorable effects with the risk of selection of resistant strains; therefore, these drugs are currently considered as second-line agents for UTI. When choosing an antibiotic, preference should be given to drugs with the narrow spectrum and minimal collateral damage, i.e., the principle of minimum sufficiency is of importance. Nitrofurans and fosfomycin trometamol are the optimal drugs in terms of efficiency and environmental safety in UTI. WHO experts consider nitrofurans as the most environmentally safe antibiotics with a minimally sufficient spectrum of activity. The environmental safety of antimicrobial therapy is an important component of preventing antibiotic resistance at the global and local levels.