The global landscape of substance use and its associated disorders is a complex and multifaceted issue that requires a nuanced and contextual understanding. Evolving terminology and classifications of substance use underscore the need for precision and the reduction of stigmatizing language in improving the quality of care. In examining the historical context, we can begin to trace the development of societal attitudes and policies towards substance use, from early temperance movements to modern harm reduction strategies. The prevalence and trends of substance use vary widely across different regions and cultures, influenced by factors such as gender, age, and cultural perceptions. Understanding these diverse perspectives is crucial in developing effective interventions and policies. Addressing substance use and its associated disorders requires a comprehensive approach that includes evidence-based interventions at both the public health and policy levels. Harm reduction measures, decriminalization efforts, and international cooperation are essential in mitigating the adverse impacts of substance use. By integrating health concerns into supply-chain efforts, improving governance of drug policy, and investing in research and education, we can work towards a more effective and humane approach to substance use globally. Perspectives and data presented in this chapter attempt to encapsulate the numerous interplaying facets of an ongoing dialog in addressing a complicated topic bridging healthcare, policy, culture, and humanity.