Cancer is a leading cause of death worldwide and is expected to remain a public health concern for years to come. Within Latin America, Uruguay has the highest colorectal cancer rates. Heeding past calls to action, in this article we provide a critical assessment of colorectal cancer needs and opportunities in Uruguay with a focus on developing a roadmap for future action. First, we provide an overview of risk factors, screening procedures and guidelines, and screening rates. Next, we provide an overview of psychosocial factors that influence colorectal cancer screening, with the goal of providing guidance for future behavioral health promotion initiatives in Uruguay. In this effort, we present four conceptual models that may be used for interventions: the ecological systems theory, informed decision-making, the health beliefs model, and the health literacy model. Subsequently, we propose using an integrated model based on the ecological systems theory and health literacy model to develop national, local, and community-based interventions to increase screening rates and lower the colorectal cancer burden in Uruguay. We close the paper with a summary and implications section, including recommendations for future research programs focused on the assessment of factors that influence screening.