A read mapper that is more than twice as fast as BWA, while achieving a mapping sensitivity similar to Stampy or Bowtie2. NextGenMap aligns reads reliably to a reference genome even when the sequence difference between target and reference genome is large, i.e. highly polymorphic genome. The software outperforms current mapping methods with respect to runtime and to the number of correctly mapped reads. NextGenMap handles automatically any read data independent of read length and sequencing technology. It may be used to map reads from nonstandard organism to a phylogenetically close reference genome or to apply it to metagenomics data.