MicroRNAs (miRNAs) are ~22nt-long single-stranded RNA molecules that form a RNA-induced silencing complex with Argonaute (AGO) protein to post-transcriptionally downregulate their target messenger RNAs (mRNAs). To understand the regulatory mechanisms of miRNA, discovering the underlying functional rules how miRNAs recognize and repress their target mRNAs is of utmost importance. To determine the functional miRNA targeting rules, previous studies extensively utilized various methods including high-throughput biochemical assays and bioinformatics analyses. However, in many cases targeting rules reported in one study fail to be reproduced in other studies, leaving the general rules for functional miRNA targeting elusive. In this review, we evaluate previously reported rules of miRNA targeting and discuss the biological impact of the functional miRNAs on gene-regulatory networks and the future direction of miRNA targeting research.