Adherence to antiretroviral medications has proven to be a challenge for individuals diagnosed with HIV infection. Nonadherence can lead to treatment failure, HIV resistance, and poor health outcomes. Many published studies have described factors associated with poor adherence, yet few have presented validated scales that could practically be applied in treatment settings to identify individuals at higher risk of nonadherence. This article explores the relationship between a revised version of the Perceived Stress Scale and nonadherence to antiretroviral therapy. The scale consists of the following items: How often in the past month have you felt that you were unable to control the important things in your life; confident in your ability to handle your personal problems; that things were going your way; and difficulties were piling up so high you could not handle them? Response options were "never or rarely," "sometimes," "often," and "mostly or always." In multivariate analysis, clients who scored in the highest quartile of perceived stress were more than twice as likely to be nonadherent at baseline and follow-up 1 and more than 5 times as likely to be nonadherent at follow-up 2 than clients in the lowest quartile of perceived stress scores.