Health literacy is emerging as a key element for successful medication management and empirical support for the efficacy of numeracy in the health context is rising as well. Little is known, however, about their unique effects among women and men. Given the importance of accurate medication management for effective treatment of HIV, the relation of these variables to medication management needs to be assessed. We therefore tested the relation of health literacy (reading comprehension) and numeracy to one's ability to manage a "mock" HIV regimen and whether men and women differed in these abilities. Results showed that women were less able than men to follow medication instructions and answer questions about the mock regimen. Numeracy mediated the relationship between gender and medication management. These findings highlight skills used in managing medication regimens and suggest avenues to target for identification and intervention in medication management among women and men with HIV.