Recent progress suggests that postreceptor mechanisms that contribute to insulin resistance of pregnancy appear to be multifactorial, but are exerted at the beta-subunit of the insulin receptor and at the level of IRS-1. Gestational diabetes mellitus represents the combination of acquired and intrinsic abnormalities of insulin action. The resistance to insulin-mediated glucose transport appears to be greater in skeletal muscle from GDM subjects than from pregnancy alone. There is also a modest but significant decrease in maximal insulin receptor tyrosine phosphorylation in muscle from obese GDM subjects. Results also suggest that increased insulin receptor serine/threonine phosphorylation and PC-1 could underlie the insulin resistance of pregnancy and pathogenesis of GDM. Whether additional defects are exerted further downstream from IRS-1 remains to be investigated.