We examined approaches used by African-American mothers and mothers of Latino descent for informal sex-related discussions with their children to inform sexually transmitted infection (STI)/HIV intervention development efforts. We recruited mothers (of children aged 12-15) from youth service agencies and a university in southern California. Fourteen focus groups were conducted: eight with African-American mothers (n = 31) and six with mothers of Latino descent (n = 24). Data were transcribed, coded for most common themes by four of the authors and reviewed for differences by gender of child. Four key themes emerged when focusing on parent-child discussions about sex: (1) sexual activity discussions took place for both sons and daughters; (2) protection from STI/HIV and pregnancy was a key topic; (3) the use of a direct, honest approach was preferred by mothers; and (4) seizing the moment was important for discussion opportunities. These data help broaden our understanding about the strategies used by African-American mothers and mothers of Latino descent for sexual health discussions with their sons and daughters. Evaluations of these for their potential impact on youth sexual health outcomes are warranted. The data can also contribute to the development of new culturally tailored parent-child communication strategies and HIV prevention interventions for young people of colour.