Knee pain is one of the most common indications for radiography in the evaluation of musculoskeletal disorders in children and adolescents. According to international guidelines, knee radiographs should be obtained when there is the suspicion of an effusion, limited motion, pain to palpation, inability to bear weight, mechanical symptoms (such as “locking”), and persistent knee pain after therapy. When indicated, radiographs can provide crucial information for the clinical decision-making process. Because of the developmental changes occurring in the knee during growth, the assessment of knee radiographs can be challenging in children and adolescents. Radiologists unfamiliar with the appearance of the knee on radiographs during skeletal maturation risk overcalling or overlooking bone lesions. Image acquisition techniques and parameters should be adapted to children. This article describes the most common challenges in distinguishing pathology from the normal appearance of knee radiographs in the pediatric population, offering some pearls and pitfalls that can be useful in clinical practice.