Autosomal recessive polycystic kidney disease (ARPKD) is a severe, typically early onset form of renal cystic disease. The care of ARPKD patients has traditionally been the purview of pediatric nephrologists for management of systemic hypertension and progressive renal insufficiency. However, the disease has multisystem manifestations and a comprehensive care strategy frequently requires a multidisciplinary team. In severely affected infants, the diagnosis often is first suspected by obstetricians when enlarged, echogenic kidneys and oligohydramnios are detected on prenatal ultrasounds. Neonatologists are central to the care of these infants, who may have respiratory compromise due to pulmonary hypoplasia and massively enlarged kidneys. Among neonatal survivors, a subset of ARPKD patients has clinically significant congenital hepatic fibrosis, which can lead to portal hypertension, requiring close monitoring by pediatric hepatologists. Surgical consultation may be sought to access pre-emptive nephrectomy to relieve mass effect, placement of dialysis access, surgical shunting procedures, and kidney and/or liver transplantation. Recent data suggest that children with ARPKD may be at risk of neurocognitive dysfunction, and may require neuropsychological referral. In addition to these morbidities, families of patients with ARPKD face decisions regarding genetic testing of affected children, testing of asymptomatic siblings, or consideration of preimplantation genetic diagnosis for future pregnancies. These issues require the input of genetic counselors, geneticists, and reproductive endocrinologists. As a result, the management of ARPKD requires the involvement of multiple subspecialists, as well as the general pediatrician, in a complex care network. In this review, we discuss the genetics of this disorder and provide an overview of the associated pathobiology; outline the spectrum of clinical manifestations of ARPKD and the management of organ-specific complications; discuss other disorders that involve genes encoding cilia-associated proteins that can clinically mimic ARPKD; review the animal models available for preclinical studies; and finally, consider future directions for potential targeted therapies.