Use of nonprescribed mood altering substances is pervasive and problematic in young adults with serious mental illnesses in community care. Fifty-eight percent of young adult clients with clearly defined schizophrenia or schizophrenia-related disorders participating in a long-term community treatment study were rated by staff or themselves as using alcohol, cannabis, or other street drugs several times a week or more. We interviewed in depth a random sample of these “significant users” to obtain their perspective on their frequencies, patterns, histories, contributing factors to, and effects of substance use and their related treatment experiences. Results revealed these clients’ substance use to be of long duration and deeply entrenched, with current use often involving multiple substances including both street drugs and substances of “everyday life” (e.g., caffeine, nicotine). Clients reported compelling reasons for use including anxiety reduction, relief of boredom, and a means for social contact. Staff and clients clearly view substance use quite differently, with the latter focusing at least as much on consequences of symptom relief as symptom exacerbation. Treatment implications are discussed.