Science advances occur through orderly steps, puzzle-solving leaps, or divergences from the accepted disciplinary matrix that occasionally result in a revolutionary paradigm shift. Key advances must overcome bias, criticism, and rejection. Examples in biological science include use of embryonic stem cells, recognition of Helicobacter pylori in the etiology of ulcer disease, and the evolution of species. Our work in vocal fold restoration reflects these patterns. We progressed through phases of tissue replacement with fillers and biological implants, to current efforts at vocal fold regeneration through tissue engineering, and face challenges of a new “systems biology” paradigm embracing genomics and proteomics.