Biopharmaceutical sales were at $160 billion in 2016. With many top revenue biopharmaceuticals coming off patent in the next 4 years, there is a tremendous rush by leading biopharmaceutical companies worldwide to launch biosimilar versions of innovator products. However, these protein drugs are extremely difficult to copy. In this viewpoint, we will discuss the various drugs slated to lose patent protection and the challenges in manufacturing these drugs using current technologies. The Food and Drug Administration's regulatory role and definitions of similarity will be discussed, and finally, the scientific challenges in mimicking a protein drug in the current patent- and innovation-driven research field will be considered.