Two specific classes of biologic macromolecules are the major targets of modern drug therapy: enzymes and receptors. The features that make enzymes attractive drug targets are the same as catalysis, specificity, and regulation (Chap. 3 ). These are reflected in the drug discovery process as: potency, selectivity, and specificity, and diversity/novelty of mechanisms Broadly, every enzyme in the metabolism is a potential target for manipulation. Its catalytic activity could be attenuated through the action of inhibitors or by targeting the expression of the active enzyme (by gene knockout or RNA interference). Enhancing/activation of enzyme activity may also be possible through overexpression or the use of specific activators. Our emphasis here is to look for ways and means to control the activity of enzyme protein already present, and not to go through genetic manipulations. Enzymes constitute the targets for almost half the drugs (including herbicides, pesticides, etc.) available in the market. Many of the top 100 drugs in use worldwide are enzyme inhibitors of one or the other kind. Although a bit dated, an excellent perspective on the mechanistic basis of enzyme-targeted drugs by Robertson (2005) provides a good starting point. This review also comes with a supplementary table containing a complete list of more than 300 drugs and their enzyme targets. Also, reviews on rational design of enzyme inhibitors as potential drugs by McLeish and Kenyon (2003) and Copeland et al. (2007) give a good account of this topic.