Creation of a flavylium polymethine dye set enabled selection of two fluorophores that match common lasers for exciting in the near-IR II region. Using these, researchers cast a broad net to catch any wavelength emission in the near-IR II region, and relied on selective excitation to multiplex; this is a paradigm shift away from multiplexing via discrimination of emission wavelengths. Excitation multiplexing with flavylium dyes is a new and exciting strategy, but not yet a perfect one; it requires discrete water soluble fluorophores, including one that is turned on at 808 nm.