Fluorescence-based systems have revolutionized the way organisms, cells, and biomolecules are visualized and detected. However, challenges that are common in these instruments, such as bleedthrough, background autofluorescence, and poor signal-to-noise ratios (S/N), can reduce performance and lead to frustration. Fortunately, performance and signal quality can be greatly improved by integrating next-generation thin-film optical filters into fluorescence-based instruments. Because proper optical filtering boosts throughput and enables wide-scale blocking, it solves problems like backscatter and poor signal quality, resulting in bright, high-contrast images of the target molecules.