This chapter provides a standardized best practice approach to sample collection and handling for the purpose of nucleic acid (NA) extraction and PCR. These methods are described through text and clearly illustrated figures. Furthermore, for those cases in which transportation of samples cannot be accomplished due to the inability to maintain the cold chain or limitations on the import of live disease agents in diagnostic samples, the chapter describes the use of FTA cards for collection transport and NA preparation of samples for PCR. This chapter also makes emphasis in the best safety practices for handling of samples/tissues to avoid unnecessary disease exposures to laboratory personnel. Finally, NA extraction best practices and methods will be briefly outlined.