MicroRNAs (miRNAs) have emerged as critical regulators in the mammalian immune system, influencing both the development and function of immune cells. Genetic ablation of miRNA machinery or loss of specific miRNAs can severely disrupt immune development and response, leading to disorders such as autoimmunity and cancer. MiRNAs control immune processes by modulating the concentrations of key cellular proteins, often within a narrow range, and by targeting multiple components of regulatory networks. This multitarget, subtle mode of control is highly efficient and versatile, and miRNAs can rapidly evolve to adapt to host-pathogen interactions. Studies in the immune system have demonstrated that miRNAs can influence T cell development, B cell differentiation, and immune responses, with specific miRNAs playing roles in lymphocyte lineage commitment, antigen receptor maturation, and immune memory. The miR-150, miR-181, and miR-17~92 clusters are notable examples of miRNA clusters that regulate multiple pathways and target proteins, highlighting the cooperative and redundant nature of miRNA functions. Additionally, miRNAs are involved in host-virus interactions, where they can either help viruses evade the immune response or participate in antiviral defense. In hematopoietic malignancies, deregulation of miRNA expression is a common theme, contributing to tumor metastasis and cancer stem cell maintenance. The unique ability of miRNAs to rapidly evolve and their dose-dependent regulation of cellular states make them attractive targets for future medical therapies.MicroRNAs (miRNAs) have emerged as critical regulators in the mammalian immune system, influencing both the development and function of immune cells. Genetic ablation of miRNA machinery or loss of specific miRNAs can severely disrupt immune development and response, leading to disorders such as autoimmunity and cancer. MiRNAs control immune processes by modulating the concentrations of key cellular proteins, often within a narrow range, and by targeting multiple components of regulatory networks. This multitarget, subtle mode of control is highly efficient and versatile, and miRNAs can rapidly evolve to adapt to host-pathogen interactions. Studies in the immune system have demonstrated that miRNAs can influence T cell development, B cell differentiation, and immune responses, with specific miRNAs playing roles in lymphocyte lineage commitment, antigen receptor maturation, and immune memory. The miR-150, miR-181, and miR-17~92 clusters are notable examples of miRNA clusters that regulate multiple pathways and target proteins, highlighting the cooperative and redundant nature of miRNA functions. Additionally, miRNAs are involved in host-virus interactions, where they can either help viruses evade the immune response or participate in antiviral defense. In hematopoietic malignancies, deregulation of miRNA expression is a common theme, contributing to tumor metastasis and cancer stem cell maintenance. The unique ability of miRNAs to rapidly evolve and their dose-dependent regulation of cellular states make them attractive targets for future medical therapies.