A rapidly expanding number of genetic mechanisms contributing to disease can be accessed via molecular analysis. In order to take full advantage of this potential for genetic diagnostics, and to monitor treatment by gene therapy and other emerging methods, a new generation of diagnostic techniques will be required. Of central importance in future analyses is the possibility to perform very large numbers of simultaneous genetic analyses in analytical devices of small linear dimensions. We have developed a new molecular probe design that is amenable to highly multiplex, specific analyses of total genomic DNA or of RNA molecules expressed in tissue samples. Here, a brief history of gene analytical procedures is presented, followed by a discussion of the properties, means of synthesis and applications of this new class of gene analytic reagents, padlock probes.