The Hindu Kush Himalaya (HKH) is a rich region in agrobiodiversity. As elsewhere in the world, agrobiodiversity is declining in this region, and this is impacting the functioning of ecosystems and has profound implications for agricultural sustainability and food security. Today, the challenge faced by the global community is how to slow or reverse the present trend of loss of agrobiodiversity to safeguard future food supplies. Taking examples from the HKH, this paper explores the link between agrobiodiversity and food security, identifies the key issues and challenges to maintaining agrobiodiversity, and explores potentials and opportunities for improving agrobiodiversity that are conducive to maintaining and increasing food security, ecosystem services, and agricultural sustainability, and thus building resilience. The paper concludes that urgent action and an integrated landscape approach are required, bringing together multiple stakeholders, and integrates agrobiodiversity in national policies and programmes. Appropriate economic measures should be developed to encourage local people to use the Himalayan biodiversity sustainably as a basis to achieve food security and agricultural sustainability.