Purpose: Low adherence to highly active antiretroviral therapy (HAART) may be the result of an implicit risk-benefit analysis in which beliefs about the necessity of HAART are balanced against the concerns about perceived side-effects. We examined to what extent perceived necessity of HAART and concerns about side-effects influenced self-reported adherence and virologic response. Methods: A total of 341 HIV-infected patients on HAART attending the outpatient clinic of 20 hospitals in the Netherlands completed a questionnaire including a measure of beliefs about medication (BMQ, Horne et al. 1999) and questions on treatment adherence. The BMQ comprises two scales assessing beliefs about the necessity of HAART and concerns about the potential side-effects. The relationship between beliefs about medication and treatment adherence and virologic response was investigated using logistic regression analyses. Results: The average time on HAART was 5 years. Patients reporting non-adherence during the past month were more likely to have a detectable viral load in the next 6 months (OR, 95% CI: 1.95, 1.11-3.41) supporting the validity of the adherence measurement. Generally, patients perceived HAART to be highly necessary. However, those with lower necessity scores were more likely to be non-adherent (OR, 95% CI: 1.63, 1.11-2.40) and to have a detectable viral load (OR, 95% CI: 1.70, 1.15-2.49). Surprisingly, concerns about adverse-effects were not associated with adherence (OR, 95% CI: 1.47, 0.96-2.26) nor with virologic response (OR, 95% CI: 1.22, 0.79-1.89). Conclusion: Our findings suggest that interventions to improve adherence to HAART should focus on patients′ implicit beliefs about the need for HAART.