This chapter introduces the major classes of plant secondary metabolites (phytochemicals): polyphenols, terpenoids, carotenoids, alkaloids, and others that serve as aquafeed supplements and their main modes of action. Since one of the main goals of supplementing aquafeeds with phytochemicals is to stimulate the immune system of farmed animals, this chapter will revisit the NF-κB pathway and its modulation by phytochemicals. In addition, this chapter will highlight issues that have not been adequately addressed or that may need to be the focus of future studies, such as (seemingly) harmful phytochemicals. These aspects also apply to the following chapters, so that this introductory chapter serves as an umbrella for the entire book and need not be repeated in the individual chapters. The issue of low levels of phytochemical supplementation is often inadequately addressed, so that differential responses of animals to low and high supplemented diets or adaptive responses are rarely considered. As a result, the range of responses is not fully recognized, and knowledge of the physiology and molecular biology of the treated animals remains incomplete. However, the genetic and epigenetic regulatory pathways of the hormetic dose range hold the credentials to sufficiently improve the dietary use of the supplements under consideration. Aspects such as the role of the gut microbiota and epigenetics as an important part of the mechanism of action will be the focus of intensive future studies. Based on an epigenetic mechanism and inspired by personalized medical nutrition, this chapter concludes with a hypothesis on how to combat harmful compounds in alternative food sources. Also, the chapter advocates that the selection of phytochemicals as aquafeed supplements be based on artificial intelligence methods rather than trial and error or adoption from ethnopharmacology