Recent reports have documented increases in unprotected intercourse (UI) and sexually transmitted diseases (STDs) among men who have sex with men (MSM) and other at-risk populations. A further consequence of persons living with HIV engaging in unprotected intercourse or shared parenteral exposures with seroconcordant partners is HIV recombination and superinfection, possibly with a drug-resistant or more pathogenic virus. The epidemiologic, clinical, and therapeutic implications of recent case reports confirming superinfection in persons living with HIV, as well as research priorities aimed at providing a more thorough understanding of the consequences of unprotected sex among HIV-infected people, are explored here.