Genetic testing is becoming a widespread practice and with human genome fully sequenced we want to develop best methods to do it. Single gene or single mutation screening is pretty much becoming a thing of the past. Similarly using just single PCR for identifying mutations, while cheap and quick, is being slowly replaced by highly multiplex tests.Targeted re-sequencing applications analyze a subset of human genes and/or mutations and report back the sequence of fragments tested. Currently there are two technologies for doing that: sequencing by hybridization or Next Generation Sequencing. I will discuss the technical aspects, sample and analysis workflows, and validation protocols for re-sequencing assays. I will also briefly review some of the currently available assays for targeted re-sequencing highlighting their advantages, disadvantages and clinical use.