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Over recent decades, the morbidity and mortality rate of infectious diseases with bacterial and fungal etiology has increased greatly. This may be due to overuse and abuse of prescription antifungal and antibacterial drugs, which causes organisms to gradually acquire the ability to overcome the drug and develop resistance. Moreover, many antimicrobials display a variety of toxicities for human use. Also, multiple resistance of bacteria to different antibiotics has caused many problems. Nowadays, the greatest challenges in hospital burn wards is Pseudomonas infection as this bacterium has become multiply resistant to commercial antibiotics. So that, the World Health Organization stated the most concerning condition in the 21st century relates to the most pan-drug-resistant strains, which are extremely resistant to most current antibiotics. As an example, Acinetobacter baumannii and Pseudomonas aeruginosa have the first ranks of antibiotic discovery priority as strains are resistant to the Carbapenem family. Also, annual rises to the number of drug resistant strains of pathogens such as Mycobacterium tuberculosis, HIV and malaria parasites are considered to be major concerns. Despite the efforts conducted in antimicrobial discovery, multiple-drug-resistant strains are still increasing much faster than novel antimicrobial innovations, resulting in demand for new antimicrobial therapies with the hope of overcoming infectious disease. This chapter will review most traditional and novel antibacterial and antifungal materials from the first discoveries to the latest antimicrobial techniques.