Background: Although Egypt is considered to be in the low epidemic stage of HIV infection yet the disease is considered as a threat because it affects young adults. Medical students need to have appropriate knowledge and attitudes about HIV and AIDS as they will play a key role in prevention and control. The aim of the study was to explore the knowledge and attitudes of medical students about HIV/AIDS. Methods: A cross-sectional study was carried out in Faculty of Medicine, Cairo University. A sample of 665 (N=665) fourth year medical students agreed to participate in the study. Data were collected using an anonymous self administered questionnaire. Descriptive and inferential statistics were employed for the data analysis using SPSS version 18.Results: Overall, students had correct knowledge about HIV and AIDS as well as positive attitude towards AIDS patients. Regarding knowledge about modes of transmission; overall the knowledge score about routes of transmission of HIV was high. The percent knowledge score was 72.1± 9.3, the median was 73.2, while the inter-quartile range was 65.9 -78.1. A few items however presented contradictory results from the overall score of the knowledge scale. Participants who reported a willingness to care for people with AIDS were significantly more knowledgeable and held more positive attitudes towards people with AIDS, while about half of the sample denied their willingness to live in the same community with AIDS patients. The primary sources of information for the participants were; their faculty (94%), and internet (44%).Conclusion: Medical curriculum programs need to be restructured to ensure that students gain the necessary accurate knowledge and appropriate attitudes about HIV and AIDS.