Progressive hyperglycemia is a characteristic of type 2 diabetes mellitus (T2DM) that poses a challenge to maintaining optimal glycemic control. Achieving glycemic control early in the course of disease can minimize or prevent serious complications. Most patients with T2DM eventually require insulin replacement therapy to attain and preserve satisfactory glucose control. For decades, the use of insulin to address the primary defect of T2DM has been a cornerstone of diabetes therapy. Insulin is indicated for patients with T2DM presenting with clinically significant hyperglycemia, and it is mandatory for patients exhibiting signs of catabolism. Insulin should be considered for patients in whom hyperglycemia persists despite attempts to control the condition through diet and exercise modifications and the use of noninsulin therapies. Many physicians delay initiation of insulin until absolutely necessary, sometimes overestimating patient concerns about its use. Modern insulin analogs, treatment regimens, and delivery devices make insulin more user friendly, and physicians can promote patient acceptance of insulin by reviewing the benefits of controlled glycated hemoglobin levels and addressing patient concerns.