Urban frontline services have recorded increases in psychostimulant-related presentations. A convenience sample of 183 street-based psychostimulant injectors recruited in April 2006 was administered the Kessler Psychological Distress Scale (K10) to assess psychological distress. Homelessness, unemployment, and recent public injection, along with gender (female) and financial and relationship problems, best predicted clinically significant K10 scores. Drug use measures were not significantly associated with distress once indicators of social marginalization were included. The risk environment of the street-based drug market accounts for much of the distress experienced in this milieu, highlighting the need for broad structural interventions, together with drug-specific responses.