Genetic diseases are hall marks of various diseases such as cancer, mental retardation, birth defects and neurodegenerative diseases. Identifying genomic alterations and the genes they contain will provide molecular targets for diagnosis and therapy. Clinical laboratories have increasingly adopted next generation sequencing (NGS) as a standard for the diagnosis of hereditary disorders. NGS methods can be used to detect either germline or somatic mutations. The use of PCR-based or hybridization-based enrichment strategies, clinical analysis on a single gene, multi-gene panels, or all known protein coding genes (exome sequencing) will be applied. The validity and utility of NGS-based panel testing has been demonstrated for a wide range of conditions including: hearing loss, vision loss, cardiovascular disorders, renal disorders, neurologic disorders, and cancer predispositions. Comparative Genome Hybridization (CGH) is a technique used in cytogenetic laboratories using chromosome metaphase spreads. Array CGH greatly improves the resolution of the technique by substituting metaphase spreads with genomic fragments or clones spotted in a microarray format. This method enables scanning and analysis of whole genome in a single experiment. This array CGH is easily amenable to automation and cheaper to perform. Until NGS became available array CGH is one of the most powerful toll in diagnostic test in clinical pathology. Whole Genome Amplification (WGA) method enables preparation of genomic DNA from rear and valuable samples like blood, fine needle aspirations, biopsies and archival samples. Development of novel methods for fast, sensitive and reliable RNA quantification has recently got increasing attention. Conventional methods for RNA analysis, like Northern and slot blot hybridization are in general time consuming, laborious and allow only relative quantification within a narrow concentration range. More novel methods for RNA analysis e.g. RT-PCR and real time RT-PCR are highly sensitive, but also slightly susceptible to experimental interferences. Sandwich Hybridization Assays (SHA) from crude cell samples or in connection to PCR have been extensively used in clinical diagnostics for detection of nucleic acids from bacteria, viruses, gene mutations and for cell typing. The presentation will discuss on the use of these genomics based diagnostic methods in health and disease.