Efficient antigen presentation is a prerequisite for the development of a T-cell-mediated immune response in vitro and in vivo. CD40-activated B cells (CD40B cells) are a promising alternative to dendritic cells as professional APCs for immunotherapy. CD40 activation dramatically improves antigen presentation by normal and malignant B cells, efficiently inducing naive and memory CD4(+) and CD8(+) T-cell responses. Moreover, CD40B cells do not only attract T cells by release of chemokines, but also home to secondary lymphoid organs. Furthermore, CD40B cells can be expanded exponentially over several weeks at high purity without a loss of antigen-presenting function, providing an almost unlimited source of cellular adjuvant. Vaccination with CD40B cells was shown in mice and dogs to induce a specific immune response. This article summarizes the achievements of intense research on CD40B cells over the last decade, as well as novel developments critical for a rapid translation into clinical application.