Gender differences in patterns and consequences of substance use, treatment-seeking, and motivation to change were examined in two samples of people with serious mental illness (SMI) and comorbid substance use disorders (SUDs): a community sample not currently seeking substance abuse treatment (N = 175) and a treatment-seeking sample (N = 137). In both groups, women and men demonstrated more similarities in the pattern and severity of their substance use than differences. However, treatment-seeking women showed greater readiness to change their substance use. Mental health problems and traumatic experiences may prompt people with SMI and SUD to enter substance abuse treatment, regardless of gender.