Genomics and transcriptomics in HIV and HIV/HCV coinfection provide basis for understanding of the host–virus interactions leading to the development of novel antiviral approaches and therapeutics. With progress of this branch of the basic science background for the personalized medicine is provided. In this review basic concepts related to the intracellular control of HIV infection are presented, key genome wide association studies related to HIV and HIV/HCV, as well as basic information on microRNAs involved in the control of both infections. Further studies of the intracellular immunity mechanisms and the interplay between antiviral defense systems, viral proteins and strategies used for the evasion of this immunity necessary for efficient viral replication in the setting of the HIV/HCV coinfection may shed an important light for the development of the novel treatment strategies. Especially important seem to be analyses of the deregulation of interferon response pathways, as it may identify molecules to be targeted in the development of future therapeutics directly blocking or negatively affecting HIV and HCV replication.