Modern veterinary medicine offers numerous options for treatment and clinicians must decide on the best one to use. Interventions causing short-term harm but ultimately benefitting the animal are often justified as being in the animal's best interest. Highly invasive clinical veterinary procedures with high morbidity and low success rates may not be in the animal's best interest. A working party was set up by the European College of Veterinary Anaesthesia and Analgesia to discuss the ethics of clinical veterinary practice and improve the approach to ethically challenging clinical cases. Relevant literature was reviewed. The 'best interest principle' was translated into norms immanent to the clinic by means of the 'open question argument'. Clinical interventions with potential to cause harm need ethical justification, and suggest a comparable structure of ethical reflection to that used in the context of in vivo research should be applied to the clinical setting. To structure the ethical debate, pertinent questions for ethical decision-making were identified. These were incorporated into a prototype ethical tool developed to facilitate clinical ethical decision-making. The ethical question 'Where should the line on treatment be drawn' should be replaced by 'How should the line be drawn?