To identify the genetic etiology of a disease of interest, disease-related characteristics (phenotypes) are often tested for association with genetic variants (genotypes). Although genetic association studies of single genetic variants have been widely performed, there has been increasing interest in studies of multiple adjacent genetic variants on one chromosome, known as a haplotype. In this review, we will provide background about the origin of haplotypes and why they can be useful in genetic studies; we will discuss approaches to determining haplotypes and performing haplotype-based genetic association studies; and we will compare single variant and haplotype-based approaches.