Over the past decade, treatment of HER2-positive breast cancer has been revolutionized with the introduction of targeted therapies. Survival in both early and advanced HER2-positive breast cancer has improved significantly. With evidence for major clinical benefit, it is imperative that health systems evaluate new treatments to maximize the value of health expenditures. Physicians, funding agencies, and policy makers are tasked with analyzing available evidence to ensure that each individual patient receives the optimal treatment in a resource-challenged environment.