Adrenal insufficiency is caused by either primary adrenal failure or by hypothalamic-pituitary impairment of the corticotropic axis which is predominantly due to long-term glucocorticoid treatment or by pituitary disease. Primary adrenal failure is a rare disease that is life-threatening when overlooked whle adrenal failure secondary to hypothalamo-pituitary disease is a common clinical problem that has serious impact on the quality of life. Recent data suggests that the health-related quality of life in many patients with adrenal insufficiency is more severely impaired than previously thought and that current hormone replacement strategies are insufficient to prevent increased morbidity and mortality due to the disease. Therefore, the optimization and careful monitoring of glucocorticoid and mineralocorticoid replacement therapy remains one of the most challenging tasks in endocrinology. Leaving treatment aside, diagnosis of adrenal insufficiency is also challenging, because the main presenting symptoms such as fatigue, anorexia, and weight loss are non-specifically associated with many other common ailments, delaying a correct diagnosis. Some pitfalls in diagnostic work-up, particularly in the identification of secondary adrenal insufficiency, make the diagnosis even more difficult. Despite the difficulties, the complications associated with adrenal insufficiency make the rapid diagnosis and proper management of adrenal failure are important tasks for all physicians. We review here current standards for clinical assessment, diagnosis and treatment of adrenal insufficiency in light of recent research findings.