microRNAs (miRNAs) are non-coding endogenous short RNAs which are involved in regulating gene expression at the post-transcriptional level. miR-15 family is increasingly found to play great roles in important cell processes, such as apoptosis, cell differentiation and stress response. Growing evidence indicates that miR-15 family members are implicated in tumor, cardiovascular disease and neurodegenerative disease. miRNAs have emerged as a new promising subset of therapeutic targets. The present paper reviewed the important function of miR-15 family and new approaches for miRNA-based therapy.