Steroid-induced posterior subcapsular cataracts (PSCs) exhibit three main distinctive characteristics: (i) association only with steroids possessing glucocorticoid activity, (ii) involvement of aberrant migrating lens epithelial cells, and (iii) a central posterior location. The first characteristic suggests a key role for glucocorticoid receptor activation and subsequent changes to the transcription of specific genes. Glucocorticoid receptor activation is associated in many cell types with proliferation, suppressed differentiation, a reduced susceptibility to apoptosis, altered transmembrane transport, and enhancement of reactive oxygen species activity. Glucocorticoids may be capable of inducing changes to the transcription of genes in lens epithelial cells that are related to many of these cellular processes. This review examines the various mechanisms that have been proposed to account for the development of PSC in the context of recent DNA array studies. Additionally, given that the glucocorticoid receptor can also engender wide-ranging indirect activities, glucocorticoids could also indirectly affect the lens through the responses of other cells within the ocular compartment and/or through effects on cells at more remote locations. These indirect mechanisms, which, for example, could be mediated through alterations to the intraocular levels of growth factors that normally orchestrate lens development and maintain lens homeostasis, are also discussed. Although the mechanism of steroid cataract induction remains unknown, glucocorticoid-induced gene transcription events in lens epithelial cells, and also other intraocular or systemic cells, likely interact to generate steroid cataracts. Finally, although evidence for glucocorticoid-protein adduct formation in the lens is inconclusive, the generation of such adducts cannot yet be discounted as a contributing factor and must necessarily be retained in discussions of the etiology of steroid cataract.