Gene targeting has become an indispensable tool for functional genomics in yeast and mouse; however, this tool is still missing in plants. This review discusses the gene targeting problem in plants in the context of general knowledge on recombination and gene targeting. An overview on the history of gene targeting is followed by a general introduction to genetic recombination of bacteria, yeast, and vertebrates. This abridged discussion serves as a guide to the following sections, which cover plant-specific aspects of recombination assay systems, the mechanism of recombination, plant recombination genes, the relationship of recombination to the environment, approaches to stimulate homologous recombination and gene targeting, and a description of two plant systems, the moss Physcomitrella patens and the chloroplast, that naturally have high efficiencies of gene targeting. The review concludes with a discussion of alternatives to gene targeting.