The mucosa represents a large surface of the human body that is in contact with the external environment. Mucosal tissues are colonized by an extremely dense and diverse micro flora of commensal bacteria, which compete with the growth of pathogenic strains. The mucosal sites continuously sample foreign material via specific cells, such as M cells and dendritic cells. Many new ways of antigen uptake have been described recently, especially by M cells and dendritic cells in the intestine. Depending on various factors, antigen presentation in the mucosa can lead to tolerance or initiation of an immune response. Mucosal vaccine strategies will certainly require eliciting specific antigen uptake because this initial step has a crucial role in controlling the outcome of immune responses.