<p>Heavy metal contamination of wastewater poses a significant threat to the environment and human health. Several activities, including industrial activities, mining operations, and agricultural practices, are primary sources of heavy metals such as cadmium (Cd), lead (Pb), iron (Fe), copper (Cu), chromium (Cr), mercury (Hg), arsenic (As), and zinc (Zn) in wastewater. These metals are persistent and non-biodegradable in the environment. They can bioaccumulate in living organisms and lead to severe health risks. Biosorbents derived from natural sources, such as agricultural wastes, microorganisms (algae, bacteria, and fungi), and nanomaterials (nano-biosorbents) offer significant potential for heavy metal removal from wastewater. Recent studies have shown marked effectiveness; for example, microalgae have achieved up to 99.9% removal efficiency for Cr(VI), whereas specific biosorbents derived from aloe vera waste have demonstrated uptake capacities of 370.4 mg g⁻¹ for U(VI) and 104.2 mg g⁻¹ for Cd(II). Innovative hydrogel biosorbents have reported even higher capacities, reaching 843.9 mg g⁻¹ for Pb(II), and magnetic nano-biosorbents have shown high removal rates, such as 95% for Hg(II), with capacities up to 256 mg g⁻¹. Biosorption mechanisms, including ion exchange, electrostatic interactions, and complexation, are discussed in this review paper to elucidate the underlying processes of metal sequestration. The efficiency of biosorption is influenced by factors such as pH, metal type, temperature, competing ions, concentration, and chemical modifications to biosorbents. Challenges related to regeneration and reuse are also addressed, highlighting the need for effective methods to ensure economic viability and support sustainable development goals (SDG 6: Clean Water and Sanitation; SDG 3: Good Health and Well-being).</p>