In chronic heart failure (CHF), neurohumoral systems, which help to maintain circulatory homeostasis, are maladaptive and responsible for disease progression and congestion in the long term. The activation of sympathetic hormones and renin-angiotensin-aldosterone system (RAAS), in addition to non-osmotic vasopressin release, up-regulation of aquoporine 2 and renal sodium transporters, and renal resistance to natriuretic peptide lead to a salt- and water-avid state. A primary decrease in cardiac output and arterial vasodilatation brings about arterial underfilling, which activates neuro-humoral reflexes and systems. The heart disease is the primum movens, but the kidney is the end organ responsible for increased tubular reabsorption of sodium and water. The most important hemodynamic alteration in the kidneys is constriction of glomerular efferent arterioles, which increases intraglomerular pressure and hence glomerular filtration rate. The resulting changes in intrarenal oncotic and hydrostatic pressures promote tubular reabsorption. Over time, a gradually falling glomerular filtration rate, due to CHF progression, medications or chronic kidney injury due to comorbidities, becomes more critical in sodium/water imbalance. Moreover, long-term use of diuretics can lead to a diuretic-resistant state, which necessitates the use of higher doses further activating RAAS, often at the expense of worsening renal function. However, every patient is a case in itself and the general pathophysiology of hydro-saline balance may be different in each subject. A mechanism can prevail over others and the kidney may have different responses to the same diuretic. So, it is necessary to customize each individual's long-term therapy, tailoring medical treatment according to clinical profiles, comorbidities and renal function, introducing active control of body weight by the patient himself, fluid restriction, a less restricted sodium intake, flexibility of diuretic doses, early and personalized ambulatory follow-up, and congestion monitoring by bioelectrical impedance vector analysis, BNP, inferior vena cava ultrasonography or echocardiographic e/e(1) ratio or pulmonary capillary wedge pressure.