Lead (Pb) is a major global environmental contaminant, particularly harmful to children, as elevated blood-lead levels can lead to developmental issues and cognitive impairments. Current clinical assessments primarily rely on blood lead level (BLL) tests, which provide only a temporary measure of Pb exposure. Pb accumulates throughout the body, including major organs and the central nervous system, making it essential to understand how BLLs correlate with systemic and cellular Pb uptake for proper treatment. However, obtaining tissue biopsies from the nervous system is often impractical in healthy individuals. While experimental models exist to explore Pb’s effects, research techniques are limited by access and cost. Advances in spatial Pb detection have occurred since the 1900s, but these have not seamlessly transitioned into biological sciences. Challenges such as sample preparation, size, and imaging parameters contribute to this gap. The review highlights the need for improved Pb detection techniques that can generate spatial information within biological samples, discusses current methods, and suggests future research directions to enhance understanding of Pb-related health conditions.