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Most viral infections result in lifelong immunity against the virus, which prevents subsequent superinfection. In the light of recent findings on recombination of different viral clades, infection with two different HIV strains is unlikely to occur during primary infection. However, it is unclear whether true superinfection occurs during chronic HIV infection. If it does occur, superinfection could constitute a risk for HIV-concordant couples, since transmission of drug-resistant or more virulent viruses may result in worsening of the disease or treatment failure. We review the available data on superinfection and conclude that HIV-discordant couples should be informed of the theoretical risk of superinfection, especially where only one partner is receiving effective antiretroviral treatment.