Comparison of DNA sequences from different species is a fundamental method for identifying functional elements, such as exons or enhancers, as they tend to exhibit significant sequence similarity due to purifying selection. Availability of whole-genome sequences for a constantly growing number of organisms makes identification of such elements within these genomes possible. There are two distinct phases in comparisons of genomic sequences: in the first, the sequences are aligned, and in the second, the resulting alignments are analyzed to find conservation signals that may be indicative of functional regions. Due to the considerable length of alignments, good visual representation techniques are a necessity for effective isolation of regions of interest. The VISTA family of tools provides biomedical investigators with a unified framework for the alignment of long genomic sequences and whole-genome assemblies, interactive visual analysis of alignments along with functional annotation, and many other comparative genomics capabilities.