Antimicrobials are a type of agent widely used to prevent various microbial infections in humans and animals. Antimicrobial resistance is a major cause of clinical antimicrobial therapy failure, and it has become a major public health concern around the world. Increasing the development of multiple antimicrobials has become available for humans and animals with no appropriate guidance. As a result, inappropriate use of antimicrobials has significantly produced antimicrobial resistance. However, an increasing number of infections such as sepsis are untreatable due to this antimicrobial resistance. In either case, life-saving drugs are rendered ineffective in most cases. The actual causes of antimicrobial resistance are complex and versatile. A lack of adequate health services, unoptimized use of antimicrobials in humans and animals, poor water and sanitation systems, wide gaps in access and research and development in healthcare technologies, and environmental pollution have vital impacts on antimicrobial resistance. This current review will highlight the natural history and basics of the development of antimicrobials, the relationship between antimicrobial use in humans and antimicrobial use in animals, the simplistic pathways, and mechanisms of antimicrobial resistance, and how to control the spread of this resistance.