Volatile substance misuse (VSM) is prevalent in the United States and associated with manifold deleterious outcomes. This review summarizes research on: (1) the prevalence of VSM in the United States and its trends since 1975, (2) population subgroups at an elevated risk for VSM, (3) key correlates of VSM, (4) psychosocial consequences of VSM, including emerging public health threats, and (5) etiological and contextual considerations of VSM use. Implications for future research and practice with volatile substance misusers in the United States are identified.