: In the proposed review, the pharmacological profile of unique, rare, and unusual fatty acids derived from natural amides is considered. These amides are produced by various microorganisms, lichens, and fungi. The biological activity of some natural fatty acid amides has been determined by their isolation from natural sources, but the biological activity of fatty acids has not been practically studied. According to QSAR data, the biological activity of fatty acids is shown, which demonstrated strong antifungal, antibacterial, antiviral, antineoplastic, anti-inflammatory activities. Moreover, some fatty acids have shown rare activities such as antidiabetic, anti-infective, anti-eczematic, antimutagenic, and anti-psoriatic activities. For some fatty acids that have pronounced biological properties, 3D graphs are shown that show a graphical representation of unique activities. These data are undoubtedly of both theoretical and practical interest for chemists, pharmacologists, as well as for the pharmaceutical industry, which is engaged in the synthesis of biologically active drugs.