Currently, there is a growing interest in the study of natural products, especially as part of drug discovery programs. Secondary metabolites can be extracted from a variety of natural sources, including plants, microbes, marine animals, insects, and amphibians. This chapter focuses principally on laboratory-scale processes of initial and bulk extraction from plant and microbial sources. With regard to plant natural products, the steps required for the preparation of the material prior to extraction, including aspects concerning plant selection, collection, identification, drying, and grinding, are detailed. The various extraction methods available (maceration, ultrasound-assisted solvent extraction, percolation, Soxhlet extraction, pressurized solvent extraction, extraction under reflux, steam distillation, and acid/based extraction) are reviewed. Regarding microbial natural products, this chapter covers issues relating to the isolation and culture of microorganisms and presents the extraction methods available for the recovery of microbial metabolites. Methods of minimizing compound degradation, artifacts formation, extract contamination with external impurities, and enrichment of extracts with desired metabolites are also examined.