Purpose of Review <p>The influence of basic biological differences between males and females has been historically overlooked. This is especially true when considering the differences in disease severity and progression brought on by exposure to toxic metals. A current area of interest is understanding how exposure to toxic heavy metals manifests differently in males and females. The present work assesses the potential sex-differences in diseases induced by arsenic, lead, cadmium, and chromium. These specific heavy metals are included in a wealth of literature supporting their induction of diseases that negatively impact health.</p> Recent Findings <p>Arsenic toxicity appears to effect males significantly more than females. This is largely due to males having decreased arsenic methylation ability compared to females. Lead is a potent neurotoxicant that induces developmental and behavioral deficits in young children. While these deficits are seen in both sexes, the specific aspects of behavior and development affected differ between males and females. Research shows females absorb more cadmium from the gastrointestinal tract, correlating with a rich history of cadmium-induced renal dysfunction. Occupational exposure is a significant factor when considering chromium toxicity. Males are much more likely to work in industrial positions where chromium exposure is common, resulting in more males suffering the consequences of chromium exposure than females.</p> Summary <p>Understanding how sex influences the pathogenesis of metal-induced diseases will allow for the elucidation of sex-specific mechanisms, which can be used to create more targeted and effective therapies to treat metal-induced diseases in males and females.</p> Graphical Abstract <p></p>