Objectives: Latinos are disproportionately vulnerable to severe COVID-19 due to workplace exposure, multigenerational households, and existing health disparities. Rolling out COVID-19 vaccines among vulnerable Latinos is critical to address disparities. This study explores vaccine perceptions of Latino families to inform culturally centered strategies for vaccine dissemination. Method: Semistructured telephone interviews with Latino families (22 mothers and 24 youth, 13-18 years old) explored COVID-19 vaccine perceptions including (1) sources of information, (2) trust of vaccine effectiveness and willingness to get vaccinated, and (3) access to the vaccine distribution. We identified thematic patterns using immersion-crystallization. Results: We found that (1) 41% expressed optimism and willingness to receive the vaccine coupled with concerns about side effects; (2) 45% expressed hesitancy or would refuse vaccination based on mistrust, myths, fear of being used as "guinea pigs," and the perceived role of politics in vaccine development; (3) families "digested" information gathered from social media, the news, and radio through intergenerational communication; and (4) participants called for community-led advocacy and "leading by example" to dispel fear and misinformation. Optimistic participants saw the vaccine as a way to protect their families, allowing youth to return to schools and providing safer conditions for frontline essential workers. Conclusions: Culturally centered vaccine promotion campaigns may consider the Latino family unit as their target audience by providing information that can be discussed among parents and youth, engaging a range of health providers and advocates that includes traditional practitioners and community health workers, and disseminating information at key venues, such as schools, churches, and supermarkets.