Studies that bridge innate immunity and various diseases are making rapid advances. Macrophages and dendritic cells play a leading role in innate immunity, using pattern recognition receptors (PRRs) to sense both pathogen invasion and danger signals. Among these PRRs, the Toll-like receptors (TLRs) play a central role in the immune response by recognizing not only pathogen-associated molecular patterns from bacteria and viruses but also damage-associated molecular patterns from dying or injured cells. These TLR family molecules facilitate not only the elimination of pathogens but also the development of various disorders, including arteriosclerosis, cancer, and metabolic syndrome. TLRs activate signaling pathways that result in the production of cytokines, chemokines, and various inducible molecules associated with the immune response. Although most components of the innate immune signaling pathways, such as the TLR family and its downstream signaling, have been identified, the physiological roles of many TLR signal-inducible proteins remain unclear. Recent studies have shown that some TLR-inducible proteins are critical in the immune response and the development of various disorders. In this review, we focus on the TLR signaling pathways and the roles of some TLR-inducible proteins.