Global demand for livestock products is increasing, driven by continued population growth and rising consumer incomes, particularly in emerging economy countries across Africa and Asia. If we are to produce more meat, milk, and eggs, using less resources, and under increased regulatory and consumer pressure, we must understand that livestock systems are intimately interconnected with the environment and play an important role in supporting the livelihoods of billions of people across the supply chain. Livestock production occurs in many forms and environments, ranging from low-input smallholder farms and pastoral systems to technologically advanced and intensive industrial systems. The challenges and opportunities facing these systems are often framed in the context of global megatrends: climate change (Godde et al., 2021), changing consumer preferences and increased public scrutiny on how and where our food is produced (Lawrence et al., 2019), increased global connectedness and trade intensification (Geyik et al., 2021), biosecurity risks (Begley et al., 2019), and the increasing adoption of digital technology (Bahlo et al., 2019). These challenges are significant and complex, and addressing them requires a multidisciplinary approach based on a sound foundation of animal science (Mayberry et al., 2021). This issue of Animal Frontiers addresses the key global challenges facing livestock production and highlights opportunities for co-learning and achieving greater impact by working together.