Local sequence alignment is a cornerstone of bioinformatics, allowing to compare the amino-acid sequences of different proteins, or the nucleotide sequences of different pieces of DNA. The Basic Local Alignment Search Tool (BLAST) has revolutionized the field of bioinformatics, and is currently implemented in all free and commercial bioinformatics packages. However, with the advent of Next Generation Sequencing (NGS) and the development of new sequencing techniques, the utility of traditional BLAST implementations is limited. CrocoBLAST combines the accuracy and general applicability of BLAST with computational efficiency, accessibility, and user experience, so that NGS data can be analyzed efficiently even when only modest computational resources are available.