Aptamers are short DNA or RNA oligonucleotides that specifically and efficiently bind to a target molecule. Since the publication of the first reports in 1990 describing the selection of aptamers, this technology aroused great interest, and it was considered as a powerful strategy for the identification of molecular tools for a wide range of applications. It has been perhaps in recent years when the aptamers’ technology has gained the recognition from the international community of its great potential for developing specific therapeutic and diagnostic tools. Among the variety of targets against which aptamers have been obtained, targeting viral RNA genomes have attracted much interest. In this context it is framed the work carried out by our research group. In this talk I briefly summarized the successful application of this technology to the selection of efficient RNA aptamers against highly conserved structural RNA domains within the human immunodeficiency virus type 1 (HIV-1) and the hepatitis C virus (HCV) genomes. We have described the selection of a 16 nt-long RNA aptamer targeting the polyA domain of the HIV-1 genome that reduces the viral particles production higher than 85% in a viral infection model in cell culture. Similarly we have isolated a collection of RNA aptamers targeting the essential CRE (cis-replication element) of the HCV genome, which yields viral replication inhibition rates higher than 90-95% in a cell culture replication system.