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Entering into the world of ancient DNA research is nontrivial. Because the DNA in most ancient specimens is degraded to some extent, the potential for contamination of ancient samples and DNA extracts with modern DNA is considerable. To minimize the risk associated with working with ancient DNA, experimental protocols specific to handling ancient specimens have been introduced. Here, I outline the challenges associated with working with ancient DNA and describe guidelines for setting up a new ancient DNA laboratory. I also discuss steps that can be taken at the sample collection and preparation stage to minimize the potential for contamination with exogenous sources of DNA.