Osteoporosis is an important and complex disorder that is highly prevalent worldwide. This disease poses a major challenge to modern medicine and its treatment is associated with high costs. Numerous studies have endeavored to decipher the pathogenesis of this disease. The clinical assessment of patients often incorporates information about a family history of osteoporotic fractures. Indeed, the observation of an increased risk of fracture in an individual with a positive parental history of hip fracture provides strong evidence for the heritability of osteoporosis. The onset and progression of osteoporosis are generally controlled by multiple genetic and environmental factors, as well as interactions between them, with rare cases determined by a single gene. In an attempt to identify the genetic markers of complex diseases such as osteoporosis, there has been a move away from traditional linkage mapping studies and candidate gene association studies to higher-density genome-wide association studies. The advent of high-throughput technology enables genotyping of millions of DNA markers in the human genome, and consequently the identification and characterization of causal variants and loci that underlie osteoporosis. This Review presents an overview of the major findings since 2007 and clinical applications of these genome-wide linkage and association studies.