Phenolic compounds are ubiquitous in plants which collectively synthesize several thousand different chemical structures characterized by hydroxylated aromatic ring(s). These compounds play several important functions in plants. They represent a striking example of metabolic plasticity enabling plants to adapt to changing biotic and abiotic environments and provide to plant products colour, taste, technological properties and putative health promoting benefits. Phenolic compounds represent the most studied phytochemicals and have been widely exploited as model systems in different areas of plant research. Initial studies in the field concerned the analytical characterization of a wide range of structures and of relevant enzymes with PAL being one of the most studied plant enzymes. This research is still active due to the complexity of the structures and the biosynthetic pathways As an example, the nature and functions of enzymes involved in lignin synthesis have been revisited several times, even in recent years. More recently, molecular biology and genomics have provided additional understanding of the mechanisms underlying the synthesis of these compounds with special emphasis on the regulation of gene expression by environmental factors. The extensive characterization of genes encoding the different enzymatic steps of flavonoid synthesis and cytochrome P450 genes have been among the most recent advances in this area. Metabolic engineering of lignins and flavonoids has been deeply investigated. Significant positive results have been obtained in both areas but the negative European opinion towards genetically modified organisms has considerably hampered potential applications. From a more basic point of view, global approaches (such as transcript and metabolite profiling) have investigated the repercussions of these engineered modulations of specific phenolics synthesis on other branches of plant metabolism. These studies have revealed a substantial and sometimes unexpected network of regulatory interactions. In the present time, the societal demand and an increasing interest for practical applications has stimulated a wide range of biological and epidemiological studies aiming at characterizing the health promoting properties of specific phenolic compounds with antioxidant activities towards cancer, cardiovascular and neurodegenerative diseases or for use in antiaging or cosmetic products. Increased emphasis on sustainable development should stimulate innovative investigations on phenolic synthesis for improving plant biomass and for a better control of plant and animal health.