Around the world, pediatric nephrologists encounter challenging clinical situations when decision-making is difficult. Ethical dilemmas occur when the best treatment choice is uncertain or when the nephrologist is constrained from providing a clearly superior treatment option due to conflict or a scarcity of resources. These include decision-making regarding burdensome treatments, disagreements between the nephrologist and parents or other healthcare providers, and inequities in access to therapies. While useful in providing grounding and a starting point, the traditional models of pediatric decision-making are challenged in pediatric nephrology. These limitations can contribute to further conflict and distress. This review will highlight the key ethical principles in ethical dilemmas encountered in clinical pediatric nephrology. We propose a stepwise decision-making framework, consisting of 5 questions, to respond using an ethically defensible process. Using case-based examples, we show how the framework will guide pediatric nephrologists in different practice settings to recognize an ethical dilemma, analyze it systematically, and reach a morally acceptable solution recognizing that this may vary by geographic location, availability of resources, and local cultural practices.