Primary goals in the treatment of type 2 diabetes mellitus (T2DM) include lowering blood glucose levels sufficiently to prevent micro- and macrovascular complications while limiting side effects, such as hypoglycemia and excessive weight gain. Patients with T2DM are typically treated initially with oral antidiabetes agents; however, as the disease progresses, most will require insulin to maintain glycemic control. Often insulin therapy is initiated with basal insulin, and the objective of this article is to present the conceptual aspects of basal insulin therapy and use these concepts to illustrate important clinical aspects. This will be accomplished within a broader contextual discussion of the normal physiologic patterns of insulin secretion, which consist of sustained levels of basal insulin production throughout the day, superimposed with bursts of insulin secretion following a meal (termed bolus or prandial insulin secretion) that slowly decay over 1 to 3 hours. Long-acting basal insulin analogs form a key component of basal-bolus therapy and provide basal support for patients with T2DM. Insulin therapy is often initiated with basal insulin, and newer long-acting analogs, such as insulin glargine and insulin detemir, provide steady, reliable basal insulin coverage in addition to significant advantages over traditional long-acting insulins. This article will integrate conceptual aspects of basal insulin therapy in the context of physiology, molecular pharmacology, and clinical implications of modern basal insulin analogs to provide a foundational understanding of basal insulin biology and physiology.