In recent years, the field of infectious diseases has been hit by the overwhelming amount of information generated while the human microbiome is being disentangled. Based on the interaction between the microbiota and the immune system, the implications regarding infectious diseases are probably major and remain a challenge. Aims This review was conceived as a comprehensive tool to provide an overview of the available evidence regarding the influence of the microbiome on infectious diseases in children. Methods We present the main findings aroused from microbiome research in prevention, diagnosis and treatment of infectious disease under a paediatric perspective, to inform clinicians of the potential relevance of microbiome‐related knowledge for translation to clinical practice. Results and Conclusion The evidence shown in this review highlights the numerous research gaps ahead and supports the need to move forward to integrating the so‐called microbiome thinking into our routine clinical practice.