This article focuses on the causes, mechanisms, prevention, modeling, and treatment (experimental and theoretical) of deactivation. The causes of deactivation are basically of three kinds: chemical, mechanical, and thermal. The five intrinsic mechanisms of catalyst decay, (
1
) poisoning, (
2
) fouling, (
3
) thermal degradation, (
4
) chemical degradation, and (
5
) mechanical failure, vary in their reversibility and rates of occurrence. Poisoning and thermal degradation are generally slow, irreversible processes while fouling with coke and carbon is generally rapid and reversible by regeneration with O
2
or H
2
. Catalyst deactivation is more easily prevented than cured. Poisoning by impurities can be prevented through careful purification of reactants. Carbon deposition and coking can be prevented by minimizing the formation of carbon or coke precursors through gasification, careful design of catalysts and process conditions and by controlling reaction conditions to minimize effects of carbon and coke formation on activity. Sintering is best avoided by minimizing and controlling the temperature of reaction. Regeneration of deactivated catalysts is possible for many catalytic processes and is widely practiced. Modeling and experimental assessment of deactivation processes are useful in providing (
1
) accelerated simulations of industrial processes, (
2
) predictive insights into effects of changing process variables on activity, selectivity, and life, (
3
) estimates of kinetic parameters needed for design and modeling, (
4
) estimates of size and cost for scale‐up of a process, and (
5
) a better understanding of the basic decay mechanisms. Accordingly, there are important economic benefits that can be derived by from investments in these activities.