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A fluorescence imaging system includes a number of optical components in the light path. Any of these components may introduce distortions of the optical wavefront. These distortions can result in negative effects on image quality such as reduced contrast in standard microscopy, or compromised resolution in high performance microscopy. In a growing number of microscopy applications, reducing wavefront distortion is critical to even achieving the intended microscopy method. It is therefore becoming ever more important to know how to specify and select optical filters that minimize wavefront aberration in order to maximize or even to enable optical system performance. This is especially true since optical filters are the most frequently updated optical elements in a microscope after initial purchase, as well as a critical component in the design of new optical systems. This white paper (1) elucidates how to optimally select optical filters for different high performance microscopy applications, and (2) provides specific guidance on choosing filters from Semrock’s extensive catalog that guarantee the wavefront distortion performance required for specific applications.