In children, joint pain is common complaint and it proves challenging for primary care physicians. The possible differential diagnoses include a wide range of disorders, from the common and benign ones to serious and even life-threating conditions. An accurate work-up of these patients is needed, with thorough patient history and a systematic physical examination as essential tools. Clarifying the nature, the site, and the duration of the pain is fundamental as well as identifying systemic symptoms such as fever, weight loss, and night sweating. We will provide a description of the different clinical presentations of such disorders, and suggest how to approach a targeted patient history and a complete physical examination, which may lead to the appropriate investigation and consequently to the correct diagnosis.