Antimicrobial resistance is one of the leading challenges in the human healthcare segment. Advances in antimicrobial resistance studies have revealed various intrinsic, adaptive or acquired factors to be involved for pathogenicity. Antimicrobial agents are either bactericidal or bacteriostatic in action and prescribed according to the mode of action. Various factors are confined for the antimicrobial activity of these agents via biochemical, mechanical, physiological and molecular mechanisms. Microbial cell expresses a number of alternates responsible for the evolution of resistance against these agent activities involving cell surface modifications, enzyme inhibitions, modifications in efflux system, protein carriers and mutations in nucleic acids. Apart from this, the successful adaptations of such microbes have also been observed with the transfer of responsible genes through miscellaneous operations such as vertical evolution, horizontal gene transfer, co-selection, compensatory and random mutation. In addition, alterations or modifications in biochemical and physiological mechanisms at cellular levels are also responsible for antibiotic resistance. This article briefly shows the present scenario of antimicrobial resistance and the alternatives to overcome this global issue in future.