The article reviews the emerging concept of target-directed microRNA degradation (TDMD), where trigger RNAs induce the destruction of specific miRNAs. TDMD occurs when trigger RNAs bind the miRNA-Argonaute (AGO) complex, recruiting the ZSWIMB E3 ubiquitin ligase, leading to AGO ubiquitination and subsequent miRNA destruction. Over 100 miRNAs are regulated by ZSWIMB in bilaterian animals, and hundreds of trigger RNAs have been computationally predicted. The review highlights recent progress in understanding the mechanism of TDMD, describes common features of trigger RNAs, outlines best practices for validating candidate miRNA-trigger RNA pairs, and discusses outstanding questions in the field. Key findings include the role of extensive pairing between the miRNA and trigger RNA, the importance of the 3' end pairing, and the structural changes in the AGO-miRNA complex that enable TDMD. The article also explores the functions of ZSWIMB in various biological processes and the challenges in identifying and validating trigger RNAs.The article reviews the emerging concept of target-directed microRNA degradation (TDMD), where trigger RNAs induce the destruction of specific miRNAs. TDMD occurs when trigger RNAs bind the miRNA-Argonaute (AGO) complex, recruiting the ZSWIMB E3 ubiquitin ligase, leading to AGO ubiquitination and subsequent miRNA destruction. Over 100 miRNAs are regulated by ZSWIMB in bilaterian animals, and hundreds of trigger RNAs have been computationally predicted. The review highlights recent progress in understanding the mechanism of TDMD, describes common features of trigger RNAs, outlines best practices for validating candidate miRNA-trigger RNA pairs, and discusses outstanding questions in the field. Key findings include the role of extensive pairing between the miRNA and trigger RNA, the importance of the 3' end pairing, and the structural changes in the AGO-miRNA complex that enable TDMD. The article also explores the functions of ZSWIMB in various biological processes and the challenges in identifying and validating trigger RNAs.