The Antimicrobial Peptide Database (APD2) has been updated and expanded, now containing 1228 entries, including 65 anticancer, 76 antiviral (53 anti-HIV), 327 antifungal, and 944 antibacterial peptides. APD2 allows users to search for peptide families, sources, posttranslationally modified peptides, and peptide binding targets. Statistical analysis shows that frequently used amino acid residues vary by peptide source, with Ala and Gly in bacterial peptides, Cys and Gly in plant peptides, and Leu, Ala, Gly, and Lys in amphibian peptides. Using these residues, database-aided peptide design was demonstrated, with GLK-19 showing higher activity against E. coli than human LL-37. APD2 was developed to promote research, education, and information exchange in antimicrobial peptides. It includes mature and active peptides, classifies them by biological activity, and provides statistical information and interfaces for peptide prediction and design. The database has been updated with over 700 new peptides, and additional search capabilities have been added for peptide families, sources, posttranslationally modified peptides, and peptide-binding targets. APD2 includes a 'name' field with extensive information, peptide synonyms, and allows searching for peptides with incomplete amino acid sequences. It also allows searching for peptides from specific life forms, such as bacteria, plants, insects, and frogs. The database includes synthetic peptides and those with known 3D structures, determined by NMR or X-ray diffraction. It also allows searching for chemically modified peptides and molecular targets, such as proteins, nucleic acids, sugars, and metal ions. APD2 also allows searching for peptides targeting specific microbes, such as anti-HIV peptides. The database includes frequently used amino acid residues in antimicrobial peptides, with Gly being common in all kingdoms. Cationic Lys is preferred over Arg in all kingdoms, while Arg and Tyr are rarely used in frog peptides. APD2 has been used to design new antimicrobial peptides, with GLK-19 showing higher activity against E. coli than human LL-37. The database is a useful tool for peptide design and provides information on the structure, activity, and mechanism of action of antimicrobial peptides. APD2 is available at http://aps.unmc.edu/AP/main.php.The Antimicrobial Peptide Database (APD2) has been updated and expanded, now containing 1228 entries, including 65 anticancer, 76 antiviral (53 anti-HIV), 327 antifungal, and 944 antibacterial peptides. APD2 allows users to search for peptide families, sources, posttranslationally modified peptides, and peptide binding targets. Statistical analysis shows that frequently used amino acid residues vary by peptide source, with Ala and Gly in bacterial peptides, Cys and Gly in plant peptides, and Leu, Ala, Gly, and Lys in amphibian peptides. Using these residues, database-aided peptide design was demonstrated, with GLK-19 showing higher activity against E. coli than human LL-37. APD2 was developed to promote research, education, and information exchange in antimicrobial peptides. It includes mature and active peptides, classifies them by biological activity, and provides statistical information and interfaces for peptide prediction and design. The database has been updated with over 700 new peptides, and additional search capabilities have been added for peptide families, sources, posttranslationally modified peptides, and peptide-binding targets. APD2 includes a 'name' field with extensive information, peptide synonyms, and allows searching for peptides with incomplete amino acid sequences. It also allows searching for peptides from specific life forms, such as bacteria, plants, insects, and frogs. The database includes synthetic peptides and those with known 3D structures, determined by NMR or X-ray diffraction. It also allows searching for chemically modified peptides and molecular targets, such as proteins, nucleic acids, sugars, and metal ions. APD2 also allows searching for peptides targeting specific microbes, such as anti-HIV peptides. The database includes frequently used amino acid residues in antimicrobial peptides, with Gly being common in all kingdoms. Cationic Lys is preferred over Arg in all kingdoms, while Arg and Tyr are rarely used in frog peptides. APD2 has been used to design new antimicrobial peptides, with GLK-19 showing higher activity against E. coli than human LL-37. The database is a useful tool for peptide design and provides information on the structure, activity, and mechanism of action of antimicrobial peptides. APD2 is available at http://aps.unmc.edu/AP/main.php.