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Purpose To utilize next generation sequencing (NGS) and identity‐by‐descent mapping to identify mutations in known and new genes in patients with autosomal recessive (ar) or isolated (i) retinitis pigmentosa (RP). Methods We employed Roche 454‐NGS to screen the exons of 111 inherited retinal disease (IRD) genes in 12 IRD patients with known compound heterozygous variants and 100 unsolved ar/i RP patients. We used identity‐by‐descent mapping and SOLiD‐NGS to identify novel genes for arRP. We carried out segration analysis in the relevant families using Sanger sequencing. Results The NGS approach enabled us to robustly identify 21/24 known IRD‐associated variants. Taking into consideration that a proportion of the RP patients was previously screened for mutations in selected genes, we could solve 55 ar/i RP cases. Mutations were identified in arRP genes (n=45), X‐linked RP genes (n=4), and autosomal dominant RP genes (n=6). In at least 4 families de novo mutations were found. Targeted NGS of exons in selected chromosomal regions based on homozygosity mapping enabled us to identify at least one novel arRP gene. The interpretation of sequence variants derived from whole genome exon (exome) sequencing heavily depends on positional information (linkage analysis, homozygosity mapping). Conclusion NGS can be used for comprehensive mutation scanning of known IRD genes and for the identification of novel IRD genes. The known RP genes contain 55% of the causative mutations. In a significant proportion of isolated patients, we identified X‐linked and de novo autosomal dominant mutations, which has important repercussions for genetic counselling. [ABSTRACT FROM AUTHOR]