PURPOSE OF REVIEW: This review explores the use of Inductively Coupled Plasma Mass Spectrometry (ICP-MS) and X-ray Fluorescence (XRF) for quantifying metals and metalloids in biological matrices such as hair, nails, blood, bone, and tissue. It provides a comprehensive overview of these methodologies, detailing their technological limitations, application scopes, and practical considerations for selection in both laboratory and field settings. By examining traditional and novel aspects of each method, this review aims to guide researchers and clinical practitioners in choosing the most suitable analytical tool based on their specific needs for sensitivity, precision, speed, and sample preparation. RECENT FINDINGS: Recent studies highlight enhanced capabilities of both ICP-MS and XRF technologies, making them more adaptable to various analytical needs. ICP-MS is renowned for its unmatched sensitivity and precision in detecting ultra-trace metals and metalloids in complex biological samples, such as lead in plasma or seawater. XRF advancements include lower detection limits and reduced sample preparation time, enabling rapid, non-destructive analyses, ideal for quick field assessments. Portable XRF analyzers have revolutionized on-the-spot testing, providing robust data without traditional wet-lab constraints. Moreover, hybrid techniques combining ICP-MS and XRF features are emerging, offering rapid and precise metal analysis for environmental monitoring, clinical diagnostics, and epidemiological studies. Matching analytical methods to specific research demands is critical. ICP-MS is the gold standard for detailed quantitative analysis in laboratories, while XRF excels in non-destructive, immediate field applications. Selection should consider sample complexity, sensitivity, speed, and cost-efficiency. Integrating ICP-MS and XRF offers a versatile approach to metals analysis, transforming practices in environmental science and healthcare diagnostics. As these technologies evolve, they are promising to expand capabilities in detecting and understanding the roles of metals and metalloids in health and the environment.