The Research Topic ‘ubiquitin and ubiquitin-like modifications in viral infection and innate immunity’ aimed to advance our knowledge and understanding of the regulation of innate immune signaling by ubiquitin and ubiquitin-like modifiers during infection, its interplay with viral proteins and the application of modern techniques to decode these interactions. Six original research papers, three mini-reviews, one review article, and one perspective article that covered various aspects of the Research Topic were eventually part of the collection.