Plants produce an extensive array of organic compounds derived from secondary metabolism that may be useful in animal nutrition because of their chemical makeup. These plant-derived bio-active compounds (PBAC), also referred to as phytonutrients or phytobiotics, have been shown to express antimicrobial activities against a wide range of bacteria, yeast, and fungi and have been investigated as alternatives to rumen modifiers, such as ionophoric antibiotics, in animal nutrition. PBAC have also been studied as inhibitors of pathogens that impact animal health and productivity, modulate the immune system, and reduce stress. A large number of in vitro, in situ, and in vivo studies on the effects of PBAC on ruminal fermentation have been published in recent years. Some reports have concluded that PBAC may inhibit deamination of amino acids and methanogenesis and shift fermentation towards propionate and butyrate. Responses, however, have been highly variable. Overall, hydrolysable and condensed tannins may offer an opportunity to reduce rumen methane production, although intake and animal productivity may be compromised. Most of the experiments with PBAC have been conducted in vitro. Although in vitro data are useful for screening purposes, the true value of PBAC for altering rumen microbial fermentation and ultimately enhancing animal production must be assessed in vivo and in long-term trials. Another, relatively new area of research is the effects of PBAC on immunity and animal health. PBAC such as garlic, curcumin, and capsicum have modulatory effects on the adaptive immune system in monogastric species and similar properties may be expected in ruminants. Studies with dairy cows have indicated that some PBAC delivered postruminally increase neutrophil activity and the numbers of immune cells related to acute phase immune response. Overall, some PBAC may be beneficial as rumen modifiers and may positively affect animal immunity, health, and productivity, but more and long-term studies are needed to fully elucidate these effects in ruminant animals.