The administration of pro re nata medications is the responsibility of the nurse. However, ethical uncertainties often happen due to the inability of incapacitated patients to collaborate with the nurse in the process of decision making for pro re nata medication administration. There is a lack of integrative knowledge and insufficient understanding regarding ethical considerations surrounding the administration of pro re nata medications to incapacitated patients. Therefore, they have been discussed in this paper and practical strategies to avoid unethical practices have been suggested. The complicated caring situation surrounding the administration of pro re nata medications is intertwined with ethical issues affecting the consideration of the patient's wishes and interventions that override them. The patient's right of autonomy and treatment refusal, surrogacy role, paternalism, and coercion are the main ethos of ethical pro re nata medication administration. Education and training can help nurses avoid legal and ethical issues in pro re nata medicines management and improve the quality and safety of healthcare. Empirical research is needed to improve our understanding of this phenomenon in the multidisciplinary environment of medicines management.