Host innate immunity represents the first line of defense against invading pathogens and shapes the course and outcome of pathogen infection. Mammals have evolved an array of highly conserved pattern recognition receptors (PRRs) that monitor the presence of “non-self” components or danger signals (Akira et al., 2006; Medzhitov, 2007). The innate immune signal transduction and viral regulation have been extensively reviewed elsewhere (Zhang et al., 2010), we therefore briefly summarize the signaling cascades that upregulate the transcription of antiviral inflammatory cytokines in response to viral infection. In higher eukaryotes, PRRs are classified into three categories according to their structural and functional conservation, including membrane-anchored C-type lectin, toll-like receptors (TLRs), and cytosolic NOD-like or RIGI-like receptors (NLRs and RLRs). Upon infection, PRRs sense pathogen-associated molecular patterns (PAMPs) that are usually pathogen structural components or replication intermediates (Akira et al., 2006; Medzhitov, 2007). While TLRs patrol extracellular and endosomal compartments, NLRs and RLRs monitor the cytosolic environment for foreign or self danger entities. Upon association with PAMPs, PRRs dimerize with their cognate adaptors (such as MyD88, TRIF, MAVS [also known as VISA, IPS-1, and CARDIF], or RIP2) that trigger the activation of two closely-related innate immune kinase complexes, IKKαβγ and TBK1-IKKe (also known as IKKi) (Sun et al., 2010). Through phosphorylation, these kinase complexes induce the activation of NFκB and interferon regulatory factors (IRFs), transcription factors that, in turn, upregulate the expression of antiviral proinflammatory cytokines and interferons (Chen et al., 1996; Mercurio et al., 1997; Fitzgerald et al., 2003; Sharma et al., 2003), thereby constituting potent antiviral innate immunity. The critical roles of these innate immune pathways have been elucidated by studies using gene knockout mice and conversely, investigations of pathogen evasion strategies that antagonize host innate immune responses. Within this short article, we will summarize our recent findings and introduce a new concept, innate immune exploitation whereby host innate immune activation is usurped by viruses to benefit their infection, for example, to promote viral replication.