In modern medical practice, clinical practice guidelines (CPGs) have supported physicians with the development of treatment plans through concise recommendations based on evidence from medical research. Yet, the growing demographics of older patients with complexity and comorbidities means that there is a group of real-world patients that CPGs may not adequately cover. These guidelines, which are primarily based on randomized controlled trials (RCTs), often have restrictive inclusion criteria and hence exclude such patients in their studies, resulting in recommendations that may not be in the patient’s best interests. Hence, when treating such patients, physicians may be required to deviate from CPGs’ recommendation in order to ensure the best patient outcome. This puts doctors in a difficult ethical dilemma: whether to follow the CPGs, deviate and risk being complained of, or not treat and refer the patient for palliative care. This article explores the ethical principles and considerations involved when physicians choose to deviate from CPGs in the interest of individualised patient care. The guiding philosophy when using CPGs should be that CPGs can guide the development of treatment plans, but are not meant to direct, dictate nor restrict doctors in clinical decisions-making.