The g:Profiler toolset is a widely used web server for functional enrichment analysis and conversions of gene lists. The 2019 update introduces significant improvements, including a modern responsive web interface, standardized API, and libraries. The toolset supports 467 species and strains, including vertebrates, plants, fungi, insects, and parasites, and can handle user-uploaded custom GMT files. g:Profiler relies on Ensembl as its primary data source and updates other data sources simultaneously. The core tool, g:GOST, performs functional enrichment analysis using the hypergeometric test, with multiple testing correction methods available. g:Convert maps gene identifiers between various namespaces, g:Orth maps orthologous genes across species, and g:SNPense maps human SNP identifiers to genes. The toolset is accessible via a web client, API, Python, and R packages, and is integrated into the Galaxy platform. The 2019 update includes a complete technical rewrite for faster and more flexible service, with interactive and customizable results, and support for custom data sources.The g:Profiler toolset is a widely used web server for functional enrichment analysis and conversions of gene lists. The 2019 update introduces significant improvements, including a modern responsive web interface, standardized API, and libraries. The toolset supports 467 species and strains, including vertebrates, plants, fungi, insects, and parasites, and can handle user-uploaded custom GMT files. g:Profiler relies on Ensembl as its primary data source and updates other data sources simultaneously. The core tool, g:GOST, performs functional enrichment analysis using the hypergeometric test, with multiple testing correction methods available. g:Convert maps gene identifiers between various namespaces, g:Orth maps orthologous genes across species, and g:SNPense maps human SNP identifiers to genes. The toolset is accessible via a web client, API, Python, and R packages, and is integrated into the Galaxy platform. The 2019 update includes a complete technical rewrite for faster and more flexible service, with interactive and customizable results, and support for custom data sources.