OBJECTIVES:  A literature review was conducted (1) to identify studies that utilized health-related quality of life (HRQoL) instruments in patients with dual diagnosis of mental illness and substance use disorder, and (2) to document the psychometric properties of the HRQoL instruments. METHODS:  The literature review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search was conducted in PubMed electronic database up to November, 2016. Selected MeSH terms included “Mental Disorder,” “Quality of Life,” and “Substance-Related Disorders.” Bibliographies of articles were screened for additional citations. The exclusion criteria included reviews, RCTs without HRQoL data, grey literature, and non-English articles. RESULTS:  A total of 35 articles were included in the qualitative synthesis of the review. From the 35 studies, 19 different instruments that assessed HRQoL in the dual diagnosis population were reported. The most commonly used measurement was the Quality of Life Interview (QOLI), which was utilized in 7 (20%) studies. All but 3 measures (MQoL, EuroQoL-5D, Cantril’s Ladder Scale) were previously tested for reliability, of which the Social Adjustment Scale Self-Report (SAS-SR) was not found to be reliable. Only SAS-SR was not previously tested for validity and 8 (42%) instruments were previously assessed for responsiveness. One measurement (MQoL) assessed all four main domains of HRQoL (physical, psychological, social, and spiritual). The amount of items each instrument contained varied from 1 (Cantril’s Ladder and SOFAS) to 143 (QOLI). CONCLUSIONS:  There are currently no instruments that are specifically designed to measure HRQoL in dual diagnosis population. The high variability of the number of instruments used in the studies demonstrate a need for a robust instrument in this vulnerable population. Since the dual diagnosis population requires specific tailoring due to their unique disease, future research could focus on creating a valid and reliable HRQoL measure.