A series of regimens based on intermediate-acting insulin given in the evening have been proposed as an alternative to conventional insulin therapy for non-insulin-dependent diabetes mellitus (NIDDM). This concept dates back to the earliest use of sustained-action insulin and has a rationale strengthened by recent physiological insights. Specifically, the predominance of fasting over postprandial hypoglycemia and occurrence of the dawn phenomenon in NIDDM argue for carefully timed overnight delivery of insulin. High nocturnal concentrations of free fatty acids in NIDDM may contribute to hepatic insensitivity to insulin and fasting hyperglycemia and can be suppressed by evening insulin. Although several clinical studies suggest that evening insulin regimens are safe and effective, their role in clinical practice is not yet established. Further study of this approach may clarify not only its proper use but also the best use of conventional strategies.