The HMMER web server provides an interactive interface for protein sequence similarity searching using probabilistic methods. HMMER3, the latest version, offers a 100-fold speed improvement over previous versions, enabling efficient profile hidden Markov model (profile HMM) searches via the web. The server allows users to search a single protein sequence, multiple sequence alignments, or profile HMMs against target databases, or a protein sequence against Pfam. It supports batch processing of up to 500 sequences and offers RESTful web services for integration into local workflows. The server is designed to cater to a range of user expertise and provides quick, intuitive results with graphical summaries. It also reports bit scores and E-values, and allows customization of results. The server uses a custom IP socket-based parallel system, hmmpgmd, to handle searches efficiently. Results can be visualized with domain graphics, hit distribution graphs, and alignment details. The server also allows retrieval of results via a unique 36-character identifier. The web server is accessible at http://hmmer.janelia.org. The server supports multiple sequence databases and provides results in various formats. It also includes tools for batch processing and result visualization. The server is designed to be user-friendly and efficient, with a focus on speed and minimizing response time. Future developments include support for the fourth protein search algorithm, jackhmmer, and improved visualization of search results using phylogenetic trees.The HMMER web server provides an interactive interface for protein sequence similarity searching using probabilistic methods. HMMER3, the latest version, offers a 100-fold speed improvement over previous versions, enabling efficient profile hidden Markov model (profile HMM) searches via the web. The server allows users to search a single protein sequence, multiple sequence alignments, or profile HMMs against target databases, or a protein sequence against Pfam. It supports batch processing of up to 500 sequences and offers RESTful web services for integration into local workflows. The server is designed to cater to a range of user expertise and provides quick, intuitive results with graphical summaries. It also reports bit scores and E-values, and allows customization of results. The server uses a custom IP socket-based parallel system, hmmpgmd, to handle searches efficiently. Results can be visualized with domain graphics, hit distribution graphs, and alignment details. The server also allows retrieval of results via a unique 36-character identifier. The web server is accessible at http://hmmer.janelia.org. The server supports multiple sequence databases and provides results in various formats. It also includes tools for batch processing and result visualization. The server is designed to be user-friendly and efficient, with a focus on speed and minimizing response time. Future developments include support for the fourth protein search algorithm, jackhmmer, and improved visualization of search results using phylogenetic trees.