Vitamins D and K are both fat-soluble vitamins and play a central role in calcium metabolism. Vitamin D promotes the production of vitamin K-dependent proteins, which require vitamin K for carboxylation in order to function properly. The purpose of this review is to summarize available evidence of the synergistic interplay between vitamins D and K on bone and cardiovascular health. Animal and human studies suggest that optimal concentrations of both vitamin D and vitamin K are beneficial for bone and cardiovascular health as supported by genetic, molecular, cellular, and human studies. Most clinical trials studied vitamin D and K supplementation with bone health in postmenopausal women. Few intervention trials studied vitamin D and K supplementation with cardiovascular-related outcomes. These limited studies indicate that joint supplementation might be beneficial for cardiovascular health. Current evidence supports the notion that joint supplementation of vitamins D and K might be more effective than the consumption of either alone for bone and cardiovascular health. As more is discovered about the powerful combination of vitamins D and K, it gives a renewed reason to eat a healthy diet including a variety of foods such as vegetables and fermented dairy for bone and cardiovascular health.