Recent evidence suggests that most of the rheumatic diseases are complex or multifactorial diseases with contributions from HLA and multiple non-HLA genes. Studies using candidate gene approach suggested that early components of the complement pathway, Fc receptor IIa, IIIa, mannose-binding lectin, IL-10 and TNFR2 might be potential non-HLA susceptibility genes to systemic lupus erythematosus, although substantial difference among populations are reported. Linkage analyses using affected sib pairs indicated several candidate regions on chromosome 1. A recently completed genome-wide linkage analysis of rheumatoid arthritis revealed a number of possible candidate regions in addition to HLA. Identification of the susceptibility genes will be accelerated along with technological advances and the accomplishment of human genome project, and will deepen our understanding of rheumatic diseases.