Although many drugs may be effective at controlling symptoms and reducing hospitalizations, the mounting cost of new medicines and the growing portion of our healthcare dollars needed to pay for them will force decision makers at all levels – payer, prescriber, and patient. This chapter describes current investigations around the extent to which Canada could reduce its overall drug expenditures by decreasing the use of expensive, heavily prescribed medications in favor of equally effective but less expensive alternatives. The cholesterol-lowering drug Lipitor is the world's top-selling drug and holds first place in almost any prescription drug budget, yet, surprisingly, it is prescribed with no evidence of superiority in preventing heart attacks and strokes over other cholesterol-lowering agents. Proton pump inhibitors (PPIs), such as Losec, Nexium, and Pantoloc, are first-line therapy in refractory cases of esophagitis or for severe erosive esophagitis.