Adenosine deaminase acting on RNA (ADAR) is a mammalian protein family, consisting of five enzymes out of which ADAR1 and ADAR2 possess catalytic activity. Their mechanism of action, called A-to-I (adenosine-to-inosine) editing, is a post-transcriptional modification on double-stranded RNA (dsRNA) molecules and occurs in both nucleus and cytoplasm of various human cell. As one of the most abundant post-transcriptional modifications on nucleic acids, A-to-I editing is associated with various pathologic conditions throughout the human body. Because of their effect on dsRNA and subsequent pathogen recognition, ADAR proteins have a pivotal role in biochemical mechanisms of interferon (IFN) induction and regulation of the innate immune response. However, the central role of ADAR proteins in immunological mechanisms means that dysregulation of their activity, be it increase or decrease, can cause some significant disruptions in the human body leading to autoimmune reaction or immunosuppression. The link between ADAR induced A-to-I editing and several cancer types is clearly present. However, in different tumors ADAR has a different role. It can act as a tumour suppressor gene through neoantigen formation or stimulate tumor development as an oncogene. Site-specific editing events in the central nervous system (CNS) are essential for the creation of glutamate and serotonin receptor subunits that make receptors impermeable to calcium. Editing in the CNS facilitates synaptic scaling and plasticity indicating that neural death by excitotoxicity is an evolutionary adaptation in case of ADAR2 failure. Moreover, dysregulation of ADAR activity is present in the neurodegenerative disease amyotrophic lateral sclerosis (ALS) and mental illnesses such as depression, bipolar disorder, schizophrenia and addiction. In a viral infection, depending on the cellular context and virus type, A-to-I editing can act both in a proviral and an antiviral manner. ADAR proteins can influence the course of viral infection in an editing-dependent or editing-independent form. In this review, we use the Epstein-Barr virus (EBV) and Hepatitis C virus (HCV) as exemplary cases to underline the essential role of ADAR in the viral life cycle.