The Endocrine Society has published clinical practice guidelines for the treatment of Cushing's syndrome (CS). The guidelines aim to provide evidence-based recommendations for managing CS, which is a condition of pathological hypercortisolism. The primary goal of treatment is to normalize cortisol levels or action to eliminate symptoms and treat associated comorbidities. Surgical resection of the causal lesion is generally the first-line treatment. For patients with ACTH-dependent CS who cannot be treated surgically, second-line options include medical therapy, bilateral adrenalectomy, and radiation therapy. The guidelines emphasize the importance of individualized treatment based on the patient's condition and the need for long-term follow-up to monitor for recurrence and manage hormonal deficiencies. Adjunctive management includes education for patients and their families, monitoring for cortisol-dependent comorbidities, and vaccinations to reduce infection risk. The guidelines also address special populations, such as those with Carney complex, and emphasize the importance of early diagnosis and treatment to reduce mortality and improve quality of life. The recommendations are based on a systematic review of the literature and are graded according to the strength of evidence and the quality of the evidence. The guidelines are intended to help clinicians make informed decisions about the treatment of CS.The Endocrine Society has published clinical practice guidelines for the treatment of Cushing's syndrome (CS). The guidelines aim to provide evidence-based recommendations for managing CS, which is a condition of pathological hypercortisolism. The primary goal of treatment is to normalize cortisol levels or action to eliminate symptoms and treat associated comorbidities. Surgical resection of the causal lesion is generally the first-line treatment. For patients with ACTH-dependent CS who cannot be treated surgically, second-line options include medical therapy, bilateral adrenalectomy, and radiation therapy. The guidelines emphasize the importance of individualized treatment based on the patient's condition and the need for long-term follow-up to monitor for recurrence and manage hormonal deficiencies. Adjunctive management includes education for patients and their families, monitoring for cortisol-dependent comorbidities, and vaccinations to reduce infection risk. The guidelines also address special populations, such as those with Carney complex, and emphasize the importance of early diagnosis and treatment to reduce mortality and improve quality of life. The recommendations are based on a systematic review of the literature and are graded according to the strength of evidence and the quality of the evidence. The guidelines are intended to help clinicians make informed decisions about the treatment of CS.