This section describes the main different NGS approaches used in pathology practice. These include targeted NGS, whole exome sequencing and whole genome sequencing. For each of those, the underlying technology and data analysis will be briefly explained. Moreover, its application in pathology (including its advantages and disadvantages) including the amount of input material, sequencing depth, risk/benefit of potential new findings, bioinformatical complexity, and costs are touched upon. This is essential because input material is often little and relatively poor on one hand, with a demanding reality (reliable and fast results against low costs containing as much preclinical information as possible). In the end, the future perspective of the value of these techniques in diagnostic pathology will be highlighted.