Glucocorticoid (GC) resistance can occur in a number of diseases. It can be either generalized (i.e., familial glucocorticoid resistance) or localized (i.e., asthma). In many cases, a reason for this resistance to steroids lies with mutations or polymorphisms present in the glucocorticoid receptor gene (GR/NR3C1) that belongs to a large family of nuclear receptors. A number of GC-resistant cell lines have been isolated in vitro, some of which arose or may have arisen in vivo. These and the mutations defined in them are included in this review as well as mutations engineered in plasmids and expressed in vitro. It also lists polymorphisms and the individual studies where association-related studies have been performed. NR3C1 is located on chromosome 5q31 and contains 10 exons that code for a 777 amino acid protein. There are two naturally occurring isoforms of the NR3C1, GRalpha (functional) and GRbeta (no hormone-binding ability). A total of 15 missense, three nonsense, three frameshift, one splice site, and two alternative spliced mutations have been reported in the NR3C1 gene associated with glucocorticoid resistance as well as 16 polymorphisms. Mutation and polymorphism data for NR3C1 will soon be found on the newly created locus-specific database.