SAMDI Affinity Selection Mass Spectrometry is a universal approach for the discovery of small molecules that bind specifically to target DNA, RNA, or proteins. RNA molecules are key players in cellular regulation, including cell signaling, gene expression and differentiation. Coding and non-coding RNA transcripts are also implicated in several human pathologies. microRNAs are single stranded noncoding RNA molecules that contribute to gene expression regulation. MircoRNAs 21 and 34 (miR-21 and miR-34) are upregulated in several cancers. Small molecules that bind to these transcripts represent novel opportunities for therapeutic intervention.