The implementation of molecular techniques, and more recently the rise of metagenomic studies applied in marine systems, has revolutionized our understanding of marine ecology, especially in microbial research. Preparation of high-quality, representative, nucleic acids from cultures and raw marine samples is the basis of all molecular approaches. Presently, many protocols are available throughout the scientific literature but due to the vast diversity of marine environments and organisms, none of them could be used as a universal protocol that can fit for all marine samples (seawater as well as sediments). The purpose of this chapter is to highlight the key points involved in the preparation of nucleic acids from marine microbial communities, from sampling to extraction. A special attention is paid to the specific challenges faced in the marine environment.