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 amphibia. This chapter focuses principally on laboratory-scale processes of initial and bulk extraction of natural products 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 methods available for solvent extraction (maceration, percolation, Soxhlet extraction, pressurized solvent extraction, ultrasound-assisted solvent extraction, extraction under reflux, and steam distillation) are reviewed. Further focus is given on the factors that can influence the selection of a method and suitable solvent. Specific extraction protocols for certain classes of compounds are also discussed. Regarding microbial natural products, this chapter covers issues relating to the isolation of microorganisms and presents the extraction methods available for the recovery of metabolites from fermentation broths. Methods of minimizing compound degradation, artifact formation, extract contamination with external impurities, and enrichment of extracts with desired metabolites are also examined.