Enzymes are deactivated by different ways to an inactive state, which is a major constraint in the development of biotechnological processes. Understanding the complex process of enzyme deactivation will be helpful in enhancing the feasibility of many biological processes. This paper mainly deals with the different ways by which enzymes are inactivated, which includes the role of thermodynamics in deactivation. Different models namely, unified deactivation theory, single exponential model, rapid equilibrium model, isozyme model and bacterial contamination model used to describe the complex deactivation processes are also discussed in this communication. The complete understanding of deactivation process is very essential in commercialization because enzyme activity and stability of the enzyme play a critical role in economics of biotechnological processes. Activity and stability of the enzyme are conflicting properties and trade-off between these factors must be considered in the selection and design of enzymes.