Cloacal exstrophy, also referred to as Omphalocele-Exstrophy-Imperforate anus-Spinal defects syndrome (OEIS), involves an anterior abdominal wall defect and a spectrum of urinary, gastrointestinal, skeletal, spinal, and genital anomalies. Prenatal diagnosis rates of cloacal exstrophy are higher than those of bladder exstrophy due to the extensive comorbidities involved. Historically, malnutrition, sepsis, and renal failure resulted in high infant mortality rates. Advances in neonatal management and surgical reconstructive techniques have led to improved survival. Patients with cloacal exstrophy require lifelong individualized care to optimize nutritional status and renal function. The increase in life expectancy has led to growing emphasis on long-term issues, such as urinary and fecal continence, health related quality of life, and sexual function.