The therapeutic importance of microRNA (miRNA) regulation has recently been realized as these small, noncoding RNAs have been demonstrated to be involved with a plethora of diseases and disorders. Due to the complex miRNA maturation process, the expression of these important biomolecules can be manipulated at various stages of the pathway. This review examines both in vivo and in vitro mechanisms and assays that have been developed to regulate miRNA levels. Modulation of miRNA maturation can be accomplished via several therapeutic agents, including small molecules and oligonucleotides, in both specific and nonspecific fashions. Due to the relevance of miRNAs, these novel therapeutic approaches represent new tools for the treatment of various cancers and other deleterious disorders.