Diabetes is a multifaceted metabolic disorder that can be caused by pancreatic β-cell destruction (type I diabetes) and/or heightened by β-cell failure (type II diabetes). The gross clinical and physiological characteristics of the disease are well characterized, and viable treatment options can drastically alter the course and effects of the disease. However, the molecular events occurring within the β-cell that cause or contribute to diabetes are not adequately understood, especially in terms of the interplay between the physiological signals that facilitate disease development. A recent report, focused on a mechanism by which IL-1β induces β-cell apoptosis, underscores the complexity of the molecular events that may cause or affect the progression of diabetes. This commentary summarizes aspects of this report, discusses an example of the complexity of β-cell regulation and proposes more frequent use of complex in vitro systems that more closely mimic in vivo conditions so that greater advances can be made toward understanding the molecular mechanisms contributing to diabetes. Understanding the molecular etiology of β-cell dysfunction will likely enhance the possibility of developing novel diabetes therapeutic interventions for diabetes.