Single nucleotide polymorphisms (SNPs) are the most common form of human genetic variation, with millions present in the human genome. Because only 1% might be expected to confer more than modest individual effects in association studies, the selection of predictive candidate variants for complex disease analyses is formidable. Technologic advances in SNP discovery and the ever-changing annotation of the genome have led to massive informational resources that can be difficult to master across disciplines. A simplified guide is needed. Although methods for evaluating nonsynonymous coding SNPs are known, several other publicly available computational tools can be utilized to assess polymorphic variants in noncoding regions. As an example, the authors applied multiple methods to select SNPs in DNA double-strand break repair genes. They chose to evaluate SNPs that occurred among a preexisting set of 57 validated assays and to justify new assay development for 83 potential SNPs in the DNA-dependent protein kinase catalytic subunit. Of the 140 SNPs, the authors eliminated 119 variants with low or neutral predictions. The existing computational methods they used and the semiquantitative relative ranking strategy they developed can be adapted to a priori SNP selection or post hoc evaluation of variants identified in whole genome scans or within haplotype blocks associated with disease. The authors show a "real world" application of some existing bioinformatics tools for use in large epidemiologic studies and genetic analyses. They also reviewed alternative approaches that provide related information.