More than 20 million Americans have type 2 diabetes. Managing blood glucose is an important component in delaying, slowing, or preventing acute and long-term diabetes complications. Numerous diabetes medications are on the market for this purpose, making it difficult for the advanced practice nurse to know where to begin. This article reviews published algorithms for glucose management of type 2 diabetes and the diabetes medication classes and agents within each class. Knowing how each class works and how to initiate, titrate, and combine diabetes medications is vital when customizing a diabetes medication regimen to meet target glycemic goals.