Heart failure is a global health concern, affecting millions of individuals worldwide. Midodrine, an alpha-1 receptor agonist, might be a potential treatment option for patients with heart failure and concurrent hypotension. This review provides a comprehensive summary of the existing literature on the use of midodrine in heart failure patients, focusing on its pharmacology, epidemiology, and public health impact. Guideline-directed medical therapy (GDMT) is essential in heart failure management, but hypotension may limit its initiation or up-titration. Studies have shown that midodrine can improve blood pressure, reduce the need for vasopressor support, and enable the prescription of GDMT in patients who are intolerant to it due to hypotension. However, there are concerns over increased all-cause mortality in some studies, small sample sizes, and nonrandomized study designs in others. Further research, including large-scale randomized controlled trials and long-term follow-up studies, is needed to better understand the risks and benefits of midodrine use in heart failure patients, particularly in relation to GDMT. Clinicians should consider the potential advantages of midodrine against the limited evidence and potential risks before incorporating it into their clinical practice for heart failure treatment.