The treatment of bacterial infections and other microbial infections is increasingly complicated by the ability of bacteria and other microbes to develop resistance to antimicrobial agents. Microbial resistance to antimicrobial agents or chemotherapeutic agents had been attributed to their ability to bypass or overcome the various mechanisms by which the said antimicrobial agents exhibit their activities against them. These mechanisms include interference with cell wall synthesis (for example, β-lactams and glycopeptide agents), inhibition of protein synthesis (macrolides and tetracyclines), interference with nucleic acid synthesis (fluoroquinolones and rifampin), inhibition of a metabolic pathway (trimethoprim-sulfamethoxazole), and disruption of bacterial membrane structure (polymyxins and daptomycin). This is because antibiotics exhibit their activities on microbes through any of these methods. Bacteria may be intrinsically resistant to first- class of antimicrobial agents, or may acquire resistance by de novo mutation or via the acquisition of resistance genes from other organisms. Acquired resistance genes confer on bacteria the ability to carry out any of the mechanism of resistance earlier stated. Acquisition of new genetic material by antimicrobial-susceptible bacteria from resistant strains of bacteria may occur through conjugation, transformation, or transduction, with transposons often facilitating the incorporation of the multiple resistance genes into the host’s genome or plasmid. Similarly, several cases of resistance to antifungal agents had been identified in clinical cases. The persistence nature of resistance to chemotherapeutic agents in both fungi and bacteria stimulates this write up. This paper tries to analyze the various mechanisms by which microorganism develop resistance in recent time and suggest the alternative solution such as the synergy between prebiotics and probiotics and the use of phytomedicine to combat this problem; including public health measures. Key words: Prebiotics, phytomedicine, fungi, bacteria, resistance.