Proper treatment of non-insulin-dependent (type II) diabetes presents the physician with a number of choices. Diet and exercise should be tried first in many patients; if this regimen is unsuccessful, treatment with either insulin or a first- or second-generation sulfonylurea must be considered. Theoretically, second-generation agents are more advantageous than first-generation agents because they do not interact with other drugs. I do not believe that they are more efficacious, however, and they probably do not have fewer side effects if chlorpropamide (Diabinese) is eliminated from consideration. Future well-designed crossover studies may help to clarify this issue. Combined insulin and sulfonylurea therapy can be tried in obese patients resistant to large doses of insulin, although results are not dramatic. In all patients the goal is to reach acceptable fasting glucose levels and near-normal glycosylated hemoglobin values.