Congestion is the most important contributor to morbidity and mortality in heart failure. In patients without congestion, maintaining a neutral sodium balance is imperative to prevent evolving volume overload. Adequate use of neurohumoral blockers, in combination with dietary sodium restriction, is essential and may preclude the need for maintenance diuretic therapy. If volume overload still prevails, loop diuretics remain the mainstay treatment to reduce excessive extracellular volume. However, combinational drug therapy might offer a more attractive alternative to achieve a balanced natriuresis, instead of further uptitration of loop diuretics. Importantly, elevated cardiac filling pressures may be caused by volume misdistribution and impaired venous capacitance, rather than absolute volume overload. Vasodilator therapy to unload the heart, increase venous capacitance, and lower arterial impedance might be interesting in such cases. This review offers a practical approach into current and potential future pharmacologic therapies for managing congestion, focusing on combinational and targeted therapy.