Insulin was isolated and used as a therapeutic agent for the first time more than 80 years ago. In subsequent decades, the structure of insulin was fully resolved and several insulin analogues were introduced in clinical practice. Important discoveries were made concerning the mechanism of action of insulin, its interaction with receptors, and insulin-dependent cellular processes. Despite all these successes, diabetes mellitus remains one of the most important human diseases with high morbidity and mortality. Therefore, studies of insulin secretion, regulation of its expression, and mechanism of action still remain important topics. The review summarizes the latest knowledge in the field.