This special issue of the Journal of Integrative Bioinformatics contains updated specifications of COMBINE standards in systems and synthetic biology. The 2021 special issue presents four updates of standards: Synthetic Biology Open Language Visual Version 2.3, Synthetic Biology Open Language Visual Version 3.0, Simulation Experiment Description Markup Language Level 1 Version 4, and OMEX Metadata specification Version 1.2. This document can also be consulted to identify the latest specifications of all COMBINE standards.