As opportunistic omnivores, humans are evolutionarily adapted to obtain calories and nutrients from both plant and animal food sources. Today, many people overconsume animal products, often-processed meats high in saturated fats and chemical additives. Alternatively, strict veganism can cause nutritional deficiencies and predispose to osteopenia, sarcopenia, and anemia. A logical compromise is a plant-rich diet with fish/seafood as principal sources of animal food. This paper reviews cumulative evidence regarding diet and health, incorporating data from landmark clinical trials of the Mediterranean diet and recommendations from recent authoritative guidelines, to support the hypothesis that a Pesco-Mediterranean diet is ideal for optimizing cardiovascular health. The foundation of this diet is vegetables, fruits, nuts, seeds, legumes, whole grains, and extra-virgin olive oil with fish/seafood and fermented dairy products. Beverages of choice are water, coffee, and tea. Time-restricted eating is recommended, whereby intermittent fasting is done for 12 to 16 h each day.