Osteoporosis is a disease characterized by fragile bones and high susceptibility to low-trauma fractures.It is a serious health problem, especially in elderly women.Bone mineral density (BMD) has been employed most com monly as the index for defining and studying osteoporosis.BMD has high genetic determination, with heritability ranging from 50% to 90%.Various genemapping approaches have been applied to identify specific genes underly ing osteoporosis, largely using BMD as the study phenotype.We review here the genetic determination of osteoporo sis as defined by BMD and discuss a fundamental issue we encounter in genetic research in osteoporosis: the choice of phenotype(s) to study.We briefly summarize and discuss advantages and disadvantages of various approaches used in genetic studies of osteoporosis.We review and discuss the current status for mapping and identification of genes for osteoporosis, including many studies from our own group for genetic epidemiology studies at DNA level, DNA microarray studies at transcriptom level and proteomics studies at proteome level.We also introduce our work in bioinformatics involved in our genetics/genomics studies highlighting the importance of data analysis and manage ment in dealing with high-throughput data.