Jonathan Shapiro (pen name “Zapiro”) can lay claim to being the world’s most important artist making work about the HIV/AIDS crisis. Producing up to seven cartoons per week for daily newspapers in a country with the highest number of HIV/AIDS cases in the world, Zapiro has been an outspoken critic of prominent South African government leaders who denied that HIV causes AIDS and who subsequently delayed the implementation of antiretroviral treatment programmes. In 2006, Zapiro produced a series of scathing cartoons depicting Jacob Zuma, who was charged and sensationally acquitted of raping a young HIV-positive woman but admitted to taking a shower after their “consensual” sex without a condom to avoid getting AIDS. At the time Zuma was the head of South Africa’s National AIDS Council; he later became the country’s president (2009–2018). Zuma sued Zapiro in an effort to censor the cartoonist. Based on a close study of Zapiro’s cartoons, archival research, and a broad-ranging interview with the cartoonist conducted by the author, this chapter examines the primary themes of Zapiro’s work, contextualises his most powerful HIV/AIDS-related cartoons, and discusses the controversies they have provoked. In doing so, it illuminates the use of satire by Zapiro as a form of resistance against the powerful institutions and discourses that shape AIDS policy.