GSNAP can align both single-end and paired-end reads as short as 14 nt and of arbitrarily long length. It can detect short- and long-distance splicing, including interchromosomal splicing, in individual reads using probabilistic models or a database of known splice sites. Our program also permits SNP-tolerant alignment to a reference space of all possible combinations of major and minor alleles, and can align reads from bisulfite treated DNA for the study of methylation state.