Although antibiotics were developed to fight infections, the emergence of new resistant markers, especially metallo-beta-lactamases (NDM-1), hampered the capability of all antibiotics of beta lactam group to treat infections caused by microorganisms carrying such resistances. The possible reason for evolving trends of new markers is mutations, which may cause delaying in the discovery of new antibiotics for treatments and hence became a great public threat. The overuse of antibiotics is one of the reasons to cause resistance, due to increase selective pressure in a specific population of bacteria allowing the resistant bacteria to bloom and the susceptible bacteria to pass away. Enzymes are evolving over a period of time by mutations in response to environmental pressure for increased stability and fitness leading to its functional changes. The activity of an enzyme and its future generations success in response to change conditions due to environmental stress and its improved physiological utility for constant perseverance is determined by these evolutionary drivers. Recent reports on antibiotic resistance has made a clear understanding of evolving status of β-lactamase enzymes, which are key player for antibiotic resistance.