CD-HIT is a very widely used program for clustering and comparing large sets of protein or nucleotide sequences. CD-HIT is very fast and can handle extremely large databases. CD-HIT helps to significantly reduce the computational and manual efforts in many sequence analysis tasks and aids in understanding the data structure and correct the bias within a dataset. The CD-HIT package has CD-HIT, CD-HIT-2D, CD-HIT-EST, CD-HIT-EST-2D, CD-HIT-454, CD-HIT-PARA, PSI-CD-HIT and over a dozen scripts. CD-HIT (CD-HIT-EST) clusters similar proteins (DNAs) into clusters that meet a user-defined similarity threshold. CD-HIT-2D (CD-HIT-EST-2D) compares 2 datasets and identifies the sequences in db2 that are similar to db1 above a threshold. CD-HIT-454 is a program to identify natural and artificial duplicates from pyrosequencing reads. The usage of other programs and scripts can be found in CD-HIT user's guide.