Financial support: FLR-G and CTD-R are supported by the CNPq, through a Productivity Research Fellowship; CTD-R is a Cientista do Nosso Estado by the FAPERJ. The Laboratório de Pesquisa em Malária (IOC), Fiocruz, is an Associated Laboratory of the INCT em Neuroimunomodulação supported by the CNPq (Project INCT-NIM 465489/2014-1), and of the Rede de Neuroinflamação do Rio de Janeiro financed by FAPERJ (Project Redes/FAPERJ 26010.002418/2019).Innate immunity refers to the mechanisms responsible for the first line of defense against pathogens, cancer cells and toxins. The innate immune system is also responsible for the initial activation of the body’s specific immune response (adaptive immunity). Innate immunity was studied and further developed in parallel with adaptive immunity beginning in the first half of the 19th century and has been gaining increasing importance to our understanding of health and disease. In the present overview, we describe the main findings and ideas that contributed to the development of innate immunity as a continually expanding branch of modern immunology. We start with the toxicological studies by Von Haller and Magendie, in the late 18th and early 19th centuries, and continue with the discoveries in invertebrate immunity that supported the discovery and characterization of lipopolysaccharide (LPS) and pattern recognition receptors that led to the development of the pattern recognition and danger theory.