Heart failure is a complex disease that interacts with other organ systems, such as the lungs, kidneys, and the liver, in a complex manner. The stages of heart failure often define the acuity and onset of disease symptoms and progression as well as treatment measures, in addition to the patient’s functional class. As the neurohormonal and compensatory mechanisms become resistant and fail guideline-directed medical therapy, more advanced therapies are required. This article outlines treatments for advanced heart failure and provides a review of guideline-directed medical therapies leading into the late stages of heart failure.