MicroRNAs (miRNAs) are 19–23 nucleotide long, evolutionarily conserved noncoding RNA molecules that regulate gene expression at the post-transcriptional level. This review summarizes the involvement of miRNAs in the differentiation and function of immune cells, anti-infective immune responses, immunodeficiencies, autoimmune diseases, anticancer immunity, and transplantation. The focus is on the translational clinical applications of miRNAs, including their use as noninvasive biomarkers for differential diagnosis, prognosis prediction, and treatment response prediction. Patient selection and response prediction to biological therapy are highlighted as promising areas. Replacement or inhibition of miRNAs offers significant therapeutic potential, with ongoing advancements in personalized management of immune dysregulation and reduced toxicity and side effects. Understanding the molecular effects of physical exercise and nutrition on the immune system can facilitate personalized lifestyle recommendations and advances in prevention. Challenges remain, but miRNA fingerprints can contribute to more personalized and effective management of immune-related disorders.MicroRNAs (miRNAs) are 19–23 nucleotide long, evolutionarily conserved noncoding RNA molecules that regulate gene expression at the post-transcriptional level. This review summarizes the involvement of miRNAs in the differentiation and function of immune cells, anti-infective immune responses, immunodeficiencies, autoimmune diseases, anticancer immunity, and transplantation. The focus is on the translational clinical applications of miRNAs, including their use as noninvasive biomarkers for differential diagnosis, prognosis prediction, and treatment response prediction. Patient selection and response prediction to biological therapy are highlighted as promising areas. Replacement or inhibition of miRNAs offers significant therapeutic potential, with ongoing advancements in personalized management of immune dysregulation and reduced toxicity and side effects. Understanding the molecular effects of physical exercise and nutrition on the immune system can facilitate personalized lifestyle recommendations and advances in prevention. Challenges remain, but miRNA fingerprints can contribute to more personalized and effective management of immune-related disorders.