It is clear that micro-RNAs (miRNAs) are emerging as key players in the control of a multitude of biological processes, from plants to animals, alongside with coding genes. The regulation of miRNA expression is tightly controlled, and often the same rules and regulations that govern coding gene expression apply also to miRNAs. Similar to coding genes, altering the levels or the temporal expression of a specific miRNA clearly affects the proper development and function of the tissue where it is expressed. In this review we discuss seminal studies, which demonstrate the importance of miRNAs in the immune system and a possible link between dysregulated miRNA expression and diseases, such as systemic lupus erythematosus (SLE) and cancer. In addition, we summarize progresses towards targeting miRNAs as therapeutic agents.