Within the past 2 years, the American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) and the American Association of Clinical Endocrinologists (AACE)/American College of Endocrinology (ACE) have revised their guidelines for the diagnosis and treatment of type 2 diabetes mellitus (T2DM). Both organizations recommend a diagnostic glycated hemoglobin (HbA1c) of >6.5% (based on a new appreciation of the relationship between glycemia and complications) and fasting plasma glucose levels or an oral glucose tolerance test. Findings from major trials of glucose control in patients with T2DM and the approval of novel medications have prompted revised treatment algorithms from both organizations. While both treatment guidelines recommend starting metformin in most patients on diagnosis of T2DM, they differ in terms of the "trigger" for treatment intensification (HbA1c≥7% and >6.5%, respectively) and which agents are preferred as second-line therapies. The ADA/EASD recommends a tiered approach to treatment, starting with well-validated second-line agents, such as sulfonylureas and basal insulin for patients unable to achieve target glucose levels with metformin. The AACE/ACE recommendations are based on the patient's HbA1c level and include a broader range of first- and second-line therapies and combinations. In addition to metformin, the ACCE/ACE treatment algorithm includes dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 agonists, thiazolidinediones, α-glucosidase inhibitors, sulfonylureas, and glinides. Both organizations advocate individualizing therapy to meet patient needs. This review highlights recent changes in the guidelines and uses a case-based format to illustrate how the current guidelines may be tailored to fit individual patient characteristics and circumstances.