Fluid retention is common in patients with heart failure (HF) and diuretics are a major source of management and stabilization. Diuretic resistance (DR) is defined as a failure to achieve therapeutically desired congestion relief despite using an appropriate diuretic dose. In this study, the underlying mechanisms of DR in HF patients are described and several currently available evidence-based strategies to mitigate this condition are provided. Specific aims were to investigate how DR occurs in patients with HF, how HF medications interfere with diuretic treatment, and what alternative methods are available for patients with DR while undergoing treatment for HF. Results provide several rationales for novel strategies used to help reach a state of euvolemia where there is a proper amount of blood in the circulatory system. These include reducing sodium intake, changing the timing of drug administration, and modifying diuretic dose.