Individuals with limited life expectancy represent a significant proportion of healthcare consumers and are usually patients with multiple diseases and high levels of frailty. Polypharmacy and the prescription of long lists of drugs are frequent in patients with reduced life expectancy and often, as the patient’s health status deteriorates, the list of drugs increases substantially as new medications are introduced to address new symptoms or complications.A key priority for healthcare professionals managing the care of these patients should be balancing the pharmacological approach to chronic diseases with the palliation of acute symptoms and complications. An important element of this process is to ensure that the benefit of any prescription decision outweighs potential risks. We reviewed the pros and cons of deprescribing drugs in individuals with limited life expectancy, how to identify the expected disease trajectory, which drugs are to be discontinued, identified some models trying to achieve rigorous deprescribing criteria, and the psychosocial effects of deprescribing in late phases of life.Deprescribing is not a one-time event but rather a continuous process that requires ongoing evaluation and monitoring. It is vital to continuously monitor and evaluate the pharmacological and non-pharmacological prescriptions for patients with chronic illnesses to align them with their goals of care and life expectancy.