Childhood tuberculosis (TB) represents an important part of the disease burden, yet its diagnosis remains challenging. This review summarizes the clinical, radiological, and bacteriological approaches to diagnose TB infection and disease in children. Fever (possibly intermittent or low grade), weight loss or failure to thrive, and a persistent cough for >2 weeks are the most important clinical signs for pulmonary tuberculosis. Extra-pulmonary TB, which might occur in over 40% of the patients, can have in addition some specific clinical symptoms or signs. Chest radiographs provide important information in many patients and advanced imaging can be applied in case of (and should be restricted to) inconclusive diagnosis. The Mantoux test is positive in up to 70% of non-immunocompromised TB patients, whereas HIV co-infection or malnourishment results in a lower reactivity. Evidence of an adult TB index case is clue for diagnosis of childhood TB in low-endemic countries. Bacteriological confirmation remains difficult and is useful for doubtful cases or when drug resistance is suspected.