Homing endonuclease genes (HEGs) are a large, phylogenetically diverse superfamily of enzymes with high specificity for especially long target sites. The public genomic sequence databases contain thousands of HEGs. This is a large and diverse arsenal of potential genome editing tools. To make use of this natural resource, one needs to identify candidate HEGs. Due to their special relationship with a host gene, it is also possible to predict their cognate target sequences. Here I describe the HomeBase algorithm that was developed to this end. A detailed description of the computational pipeline is provided with emphasis on technical and methodological caveats of the approach.