Male infertility accounts for approximately 50% of the cases of sterile human couples, and in many instances the genetic or molecular defects involved remain unknown. Studies conducted in animal models have elucidated the key role played by RNA-binding proteins and by the posttranscriptional regulation of gene expression during spermatogenesis. Ablation of proteins involved in each of the steps required for the processing and the utilization of messenger RNAs impairs the production of fertile spermatozoa. Recent evidence indicates that the RNA-binding protein Sam68 is absolutely required for the correct progression of spermatogenesis and for male fertility in the mouse. Sam68 belongs to the evolutionary conserved signal transduction and activation of RNA (STAR) family of RNA-binding proteins. The members of this family have been demonstrated to play crucial roles in cell differentiation and development, including male and female gametogenesis. In this review we will summarize the observations gathered on the functions of STAR proteins in different organisms, with particular emphasis on the role of Sam68 in male fertility.