One third of heart failure admissions may be complicated by acute kidney injury, resulting in a three-fold increase in length of stay and a greater likelihood of rehospitalization. Cardio-Renal syndrome type 1 refers to acute decompensation of cardiac function leading to acute renal failure. It often complicates acute coronary syndrome and acute decompensated heart failure. Both components of the syndrome contribute to morbidity and mortality. The pathophysiology of renal dysfunction is complex. Reduced cardiac output, passive congestion of the kidneys, and increased intra-abdominal pressure may contribute to the disorder. The heart, kidneys, renin-angiotensin system, sympathetic nervous system, immune system, and vasculature interact through intricate feedback loops. An imbalance in this complex system often will cause deterioration in both cardiac and renal function. Appreciation of these interactions is crucial to understanding the overall burden of disease, as well as its natural history, risk factors, associated morbidity and mortality, and therapeutic implications.