GemSIM is most suited to simulating resequencing or metagenomic projects where known reference sequences exist, as it relies on the presence of a reference sequence to initially generate reads (error models are then superimposed on top of the read). For example, GemSIM can be used in a deep resequencing project to establish at which coverage any further sequencing may not provide any increase in SNP detection accuracy. GemSIM may also prove itself valuable in developing and benchmarking de-novo assemblers, by assessing how well a known genome can be reconstructed from simulated reads. By providing a manually modified reference genome to GemSIM, users could also simulate reads to assess the detection of large genomic rearrangements via de-novo assembly.