Many foods in our diets such as berries, tea, chocolate and wine contain flavonoids, which are natural components of plants. A substantial body of evidence supports the role of flavonoids in providing protection against cardio-metabolic diseases and disorders. Despite the nearly exponential growth in flavonoid research in the past 20 years, limited progress has been made in understanding how these dietary components work. Research initially focused on their antioxidant activity without taking into account their metabolism, which now appears extensive. This has provided a new research impetus to understand the biological activity of the flavonoid metabolites. Here, we outline recent research, which suggests a highly complex interplay between metabolism, intestinal microflora, the immune system and various tissues of our body.