Unhealthy substance-use behaviors, including a heavy alcohol intake, illicit drug use, and cigarette smoking, are engaged in by many HIV-positive individuals, often as a way to manage their disease-related symptoms. This study, based on data from a larger randomized controlled trial of an HIV/AIDS symptom management manual, examines the prevalence and characteristics of unhealthy behaviors in relation to HIV/AIDS symptoms. The mean age of the sample (n = 775) was 42.8 years and 38.5% of the sample was female. The mean number of years living with HIV was 9.1 years. The specific self-reported unhealthy substance-use behaviors were the use of marijuana, cigarettes, a large amount of alcohol, and illicit drugs. A subset of individuals who identified high levels of specific symptoms also reported significantly higher substance-use behaviors, including amphetamine and injection drug use, heavy alcohol use, cigarette smoking, and marijuana use. The implications for clinical practice include the assessment of self-care behaviors, screening for substance abuse, and education of persons regarding the self-management of HIV.