Natural products are a class of chemical compounds that are biosynthesized by living organisms, including humans. Endogenous natural products are produced by human cells as well as by the human microbiome. This contribution describes the current understanding and recent progress made on endogenous natural products that are produced by human cells, including amines, steroids, and fatty acid-derived natural products. The co-metabolism and natural product produced by the human microbiome will also be described, including the involvement of tryptophan, bile acids, choline, and cysteine. New strategies and technologies have been introduced that can be applied to identify and characterize those natural products produced by the human microbiome in terms of their composition and physiological function.