Insulin resistance is a heterogenous condition with high prevalence in medical practice. As diabesity reaches epidemic levels worldwide, the role of insulin resistance is getting great importance. Contribution of risk factors like sedentary lifestyle, diets high in saturated fats and refined carbohydrates leads to this state with significant consequences. Besides its role in diabetes, insulin resistance is also associated with other several endocrine diseases, having not only a role in their development, but also to their treatment approach, evolution and even prognosis. The present review summarizes the current literature on the clinical significance of insulin resistance, as well as the possible underlying mechanisms and treatment options in order to achieve a high quality of life of these categories of patients. Deepening the role of inflammatory cytokines involved in insulin resistance paves the way for future research findings in this continuously evolving field.