Collective antibiotic drug resistance is a global threat, especially with respect to Gram-negative bacteria. The low permeability of the bacterial outer cell wall has been identified as a challenging barrier that prevents a sufficient antibiotic effect to be attained at low doses of the antibiotic. The Gram-negative bacterial cell envelope comprises an outer membrane that delimits the periplasm from the exterior milieu. The crucial mechanisms of antibiotic entry via outer membrane includes general diffusion porins (Omps) responsible for hydrophilic antibiotics and lipid-mediated pathway for hydrophobic antibiotics. The protein and lipid arrangements of the outer membrane have had a strong impact on the understanding of bacteria and their resistance to many types of antibiotics. Thus, one of the current challenges is effective interpretation at the molecular basis of the outer membrane permeability. This review attempts to develop a state of knowledge pertinent to Omps and their effective role in solute influx. Moreover, it aims toward further understanding and exploration of prospects to improve our knowledge of physicochemical limitations that direct the translocation of antibiotics via bacterial outer membrane. © 2018 Ghai and Ghai.