Heart failure (HF) is one of the most common cardiovascular diseases, bearing a significant burden of morbidity, mortality, and disability. Low serum chloride (Cl) levels have been observed to play an important role in predicting mortality and planning management strategies for HF. This review aims to investigate the influence of hypochloremia on individuals suffering from HF and its correlation with various underlying pathophysiological mechanisms. We conducted a literature review of articles published in the past 10 years, employing specific keywords to identify relevant studies from databases such as PubMed, Google Scholar, EBSCO, and Biomed Central. There is a significant paucity of studies relevant to low serum Cl levels in patients with HF. We found that hypochloremia is commonly observed in HF cases, an often overlooked aspect in clinical setting, and is associated with poor outcomes. Substantial evidence supports the notion that hypochloremia can worsen HF, reduce the response to guideline-mediated therapies, and increase mortality. Hypochloremia activates numerous neurohormonal mechanisms, further worsening the cardiorenal circuit in HF. Furthermore, low Cl levels are associated with the development of diuretic resistance, making HF difficult to manage, particularly with loop diuretics. Studies reveal associations between hypochloremia and various kinases, with a particular emphasis on with-no-lysine kinases. These kinases, involved in regulating salt and water reabsorption, exacerbate the condition when Cl levels are low. Notably, a low serum Cl level is associated with high mortality in HF and worsens the condition. HF with hypochloremia poses challenges in treatment and should, therefore, be considered in management.