Transition metals play crucial roles in biological systems, serving as essential cofactors for enzymes and participating in various physiological processes. However, their high reactivity can also make them toxic at high concentrations. Bacteria must regulate the levels of these metals to meet their physiological needs while avoiding harm. Host organisms, including humans, exploit the essentiality and toxicity of transition metals to defend against bacterial infections through a process known as "nutritional immunity." This review discusses the established and emerging paradigms in nutrient metal homeostasis at the pathogen-host interface, focusing on iron (Fe), manganese (Mn), zinc (Zn), and copper (Cu). Fe is the most abundant transition metal in the human body and is critical for bacterial pathogens, leading to mechanisms in both hosts and pathogens to limit Fe availability. Mn and Zn are also vital for bacterial physiology, and their sequestration is a key component of host defense. The review highlights the mechanisms by which hosts restrict Fe, Mn, and Zn, as well as how pathogens acquire these metals or exploit host defenses to overcome them. Additionally, it explores the role of Cu in antibacterial activity and its acquisition and detoxification by bacteria. The evolutionary perspectives on nutritional immunity and the clinical and industrial applications of understanding these mechanisms are also discussed.Transition metals play crucial roles in biological systems, serving as essential cofactors for enzymes and participating in various physiological processes. However, their high reactivity can also make them toxic at high concentrations. Bacteria must regulate the levels of these metals to meet their physiological needs while avoiding harm. Host organisms, including humans, exploit the essentiality and toxicity of transition metals to defend against bacterial infections through a process known as "nutritional immunity." This review discusses the established and emerging paradigms in nutrient metal homeostasis at the pathogen-host interface, focusing on iron (Fe), manganese (Mn), zinc (Zn), and copper (Cu). Fe is the most abundant transition metal in the human body and is critical for bacterial pathogens, leading to mechanisms in both hosts and pathogens to limit Fe availability. Mn and Zn are also vital for bacterial physiology, and their sequestration is a key component of host defense. The review highlights the mechanisms by which hosts restrict Fe, Mn, and Zn, as well as how pathogens acquire these metals or exploit host defenses to overcome them. Additionally, it explores the role of Cu in antibacterial activity and its acquisition and detoxification by bacteria. The evolutionary perspectives on nutritional immunity and the clinical and industrial applications of understanding these mechanisms are also discussed.