The pattern recognition theory proposed by the late Charles Janeway, Jr. 20 years ago provided a conceptual framework for our current understanding of the innate immune recognition and its role in the activation of adaptive immunity. Discovery of several families of pattern recognition receptors and their roles in mammalian immunity provided experimental support for the Janeway's theory. In addition to pattern recognition, there are other forms of innate immune sensing, which presumably work in specific combinations depending on the pathogen class and the type of the immune response they elicit. Here, the development of the Janeway's theory is discussed in the context of the advances made in field of innate immune recognition over the past two decades.