The ubiquitin proteasome pathway (UPP) is a versatile regulatory mechanism that allows plants to quickly react and acclimatize to changing environmental conditions. E3 ligases are the key regulatory elements that provide specificity to the pathway. This review provides a brief overview about the pathway and the specific classes of E3 ligases described in plants. The main focus of this review, however, is how the pathway provides opportunities to develop novel drugs and technological tools for research and agricultural industries. This is exemplified by how pathogens already utilize the pathway, and also the recent novel technological developments that have occurred in the last years, ranging from PROTACs, CRISPR/Cas9 or the N-degron pathway, and to what extent these approaches may be applicable for plants in today’s and future research to develop new tools and novel applications toward improvement of plant growth and performance.