The 70kDa ribosomal protein S6 kinases, S6K1 and S6K2 are two highly homologous serine/threonine kinases that are activated in response to growth factors, cytokines and nutrients. The S6 kinases have been linked to diverse cellular processes, including protein synthesis, mRNA processing, glucose homeostasis, cell growth and survival. Studies in model organisms have highlighted the roles that S6K activity plays in a number of pathologies, including obesity, diabetes, ageing and cancer. The importance of S6K function in human diseases has led to the development of S6K-specific inhibitors by a number of companies, offering the promise of improved tools with which to study these enzymes and potentially the effective targeting of deregulated S6K signalling in patients. Here we review the current literature on the role of S6Ks in the regulation of cell growth, survival and proliferation downstream of various signalling pathways and how their dysregulation contributes to the pathogenesis of human diseases.