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Advancement and developments in enzyme technology has increased the demand for extremozymes in various industries. Applications of extremozymes, especially as detergent additives have tremendously increased due to their distinct properties. Extremophiles from various geographical locations were explored for extremozymes and studied for detergent compatibility. Enzymes produced by psychrophiles, alkaliphiles, and thermophiles were extensively tested for detergent compatibility having higher catalytic activity, stability to improve the efficiency of detergents. Extremozymes such as proteases, lipases, amylases, and cellulase were reported with exceptional characteristics are considered as the primary choice for detergent additive. Additionally, mannanase, pullulanase, and pectinase were also widely used in detergent applications. Techniques in molecular biology including gene coding, sequencing of amino acids, and protein engineering gave more clarifications, revealed the compatibility issues, and helped to overcome it. Increasing thermal stability and compatibility of enzymes with chemical agents in detergents has been altered using modern methods to overcome the challenges for producing sustainable and eco-friendly detergents. In this chapter, an overview of developments in extremozymes in detergents applications, their properties and molecular approaches are discussed.