The ultimate goal of current chlamydial vaccine efforts is to utilise either conventional or modern vaccinology approaches to produce a suitable immunisation regimen capable of inducing a sterilising, long-lived heterotypic protective immunity at mucosal sites of infection to curb the severe morbidity and worldwide prevalence of chlamydial infections. This lofty goal poses tremendous challenges that include the need to clearly define the relevant effectors mediating immunity, the antigens responsible for inducing these effectors, the anti-chlamydial action(s) of effectors, and establishment of the most effective method of vaccine delivery. Tackling these challenges is further compounded by the biological complexity of chlamydia, the existence of multiple serovariants, the capacity to induce both protective and deleterious immune effectors, and the occurrence of asymptomatic and persistent infections. Thus, novel molecular, immunological and genetic approaches are urgently needed to extend the frontiers of current knowledge, and develop new paradigms to guide the production of an effective vaccine regimen. Progress made in the last 15 years has culminated in various paradigm shifts in the approaches to designing chlamydial vaccines. The dawn of the current immunological paradigm for antichlamydial vaccine design has its antecedence in the recognition that chlamydial immunity is mediated primarily by a T helper type1 (Th1) response, requiring the induction and recruitment of specific T cells into the mucosal microenvironment. Additionally, the ancillary role of humoral immune response in complementing the Th1-driven protective immunity, through ensuring adequate memory and optimal Th1 response during a reinfection, has been recognised. With continued progress in chlamydial genomics and proteomics, select chlamydial proteins, including structural, membrane and secretory proteins, are being targeted as potential subunit vaccine candidates. However, the development of an effective adjuvant, delivery vehicle or system for a potential subunit vaccine is still an elusive objective in these efforts. Promising delivery vehicles include DNA and virus vectors, bacterial ghosts and dendritic cells. Finally, a vaccine still represents the best approach to protect the greatest number of people against the ocular, pulmonary and genital diseases caused by chlamydial infections. Therefore, considering the urgency and the enormity of these challenges, a partially protective vaccine preventing certain severe sequelae would constitute an acceptable short-term goal to controlChlamydia. However, more research efforts and support are needed to achieve the worthy goal of protecting a significant number of the world’s population from the devastating consequences of chlamydial invasion of the human mucosal epithelia.