Over the past few years, acute worsening of renal function has emerged as a powerful and independent predictor of adverse cardiac outcomes among patients hospitalized with acute heart failure exacerbation. This phenomenon has been recently termed acute cardio-renal syndrome. Acute cardio-renal syndrome is not uncommon, affecting roughly one third of acute decompensated heart failure patients. The mechanism of acute cardio-renal syndrome is poorly understood and difficult to elucidate in light of the complex and multifactorial comorbidities associated with acute heart failure syndrome. Acute cardio-renal syndrome is commonly explained by hypoperfusion of the kidney with intravascular volume depletion, hypotension and low flow state ("pre-renal syndrome"). This perception, however, is challenged by the actual hemodynamics present during acute cardio-renal syndrome characterized by hypervolemia, normal cardiac output, and elevated filling pressures of the systemic and venous circulation. This review discusses the long-standing and unnoticed evidence in support of the notion that right-sided failure with raised filling pressure of the renal vein by itself can indeed lead to acute worsening renal function with oliguria, azotemia, and reduced glomerular filtration rate.