The treatment of infection with Mycobacterium tuberculosis in young children is supported by universal policy based on strong rationale and evidence of effectiveness, but has rarely been implemented in tuberculosis endemic countries. Areas covered: This review highlights a number of important recent developments that provide an unprecedented opportunity to close the policy-practice gap, as well as ongoing needs to facilitate implementation under programmatic conditions and scale-up. Expert commentary: The WHO's End TB Strategy and Stop TB Partnership's Plan to End TB provide ambitious targets for prevention at a time when National Tuberculosis Programs in tuberculosis endemic countries are increasing attention to the challenges of management and prevention of tuberculosis disease in children. This opportunity is greatly enhanced by recent evidence of the effectiveness of shorter, simpler and safer regimens to treat tuberculosis infection. The scale of the challenge for implementation will require a decentralized, integrated, community-based approach. An accurate and low-cost point-of-care test for tuberculous infection would be a major advance to support such implementation. Specific guidance for the treatment of infection in young child contacts of multidrug-resistant tuberculosis cases is a major current need while awaiting further evidence.