The PSIPRED Protein Analysis Workbench, a renowned web service for protein prediction and annotation, has been updated to enhance its functionality and performance over the past 20 years. The primary focus of the recent upgrades has been to accelerate analyses in response to the increasing size of protein sequence databases. Key improvements include a new workflow management platform that simplifies the addition of new predictive tools, a redesigned website using modern web frameworks, and enhanced hardware infrastructure. The new website provides a more intuitive layout for accessing and interpreting results, while the backend improvements, such as the use of HHBlits for sequence searching and result caching, have significantly reduced runtimes and queue times. Additionally, the PSIPRED Workbench now offers updated algorithms for protein secondary structure prediction (PSIPRED 4), GO term prediction (FFPRED 3), contact prediction (MetaPSICOV 2), disordered region prediction (DISOPRED 3), and homology modeling (DomSerf 2.1 and BioSerf 2). These enhancements ensure that the PSIPRED Workbench remains a robust and user-friendly resource for the next 20 years.The PSIPRED Protein Analysis Workbench, a renowned web service for protein prediction and annotation, has been updated to enhance its functionality and performance over the past 20 years. The primary focus of the recent upgrades has been to accelerate analyses in response to the increasing size of protein sequence databases. Key improvements include a new workflow management platform that simplifies the addition of new predictive tools, a redesigned website using modern web frameworks, and enhanced hardware infrastructure. The new website provides a more intuitive layout for accessing and interpreting results, while the backend improvements, such as the use of HHBlits for sequence searching and result caching, have significantly reduced runtimes and queue times. Additionally, the PSIPRED Workbench now offers updated algorithms for protein secondary structure prediction (PSIPRED 4), GO term prediction (FFPRED 3), contact prediction (MetaPSICOV 2), disordered region prediction (DISOPRED 3), and homology modeling (DomSerf 2.1 and BioSerf 2). These enhancements ensure that the PSIPRED Workbench remains a robust and user-friendly resource for the next 20 years.