The use of Lactococcus lactis in novel biomedical applications is a fast evolving area of interest. Quite distinct from its traditional use in the dairy industries, L. lactis has emerged as a potential delivery vector for various antigens as well as therapeutic and immunomodulatory proteins. Many recent studies have shown promising results using in vitro or animal models. In addition, the oral administration of human interleukin 10 (hIL-10)-secreting L. lactis for the management and treatment of inflammatory bowel disease (IBD) has been the subject of recent clinical trials. These trials represent the first steps for the use of genetically modified L. lactis in clinical practice. In the present review we discuss some of the recent studies which investigate the use of L. lactis as an in vivo protein delivery system. The concept of biological containment in L. lactis using pyrimidine synthesis knock-out systems is also discussed. Finally we describe recent work evaluating living versus dead L. lactis vectors with particular emphasis on the use of Gram-positive Enhancer Matrix (GEM) particles as a novel delivery system.